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Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review

  • Abdul Waris EMAIL logo , Misbahud Din , Asmat Ali , Shakeeb Afridi , Abdul Baset , Atta Ullah Khan and Muhammad Ali EMAIL logo
Published/Copyright: January 20, 2021
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Open Life Sciences
From the journal Open Life Sciences Volume 16 Issue 1

Abstract

Nanotechnology is the fabrication, characterization, and potential application of various materials at the nanoscale. Over the past few decades, nanomaterials have attracted researchers from different fields because of their high surface-to-volume ratio and other unique and remarkable properties. Cobalt and cobalt oxide nanoparticles (NPs) have various biomedical applications because of their distinctive antioxidant, antimicrobial, antifungal, anticancer, larvicidal, antileishmanial, anticholinergic, wound healing, and antidiabetic properties. In addition to biomedical applications, cobalt and cobalt oxide NPs have been widely used in lithium-ion batteries, pigments and dyes, electronic thin film, capacitors, gas sensors, heterogeneous catalysis, and for environmental remediation purposes. Different chemical and physical approaches have been used to synthesize cobalt and cobalt oxide NPs; however, these methods could be associated with eco-toxicity, cost-effectiveness, high energy, and time consumption. Recently, an eco-friendly, safe, easy, and simple method has been developed by researchers, which uses biotic resources such as plant extract, microorganisms, algae, and other biomolecules such as starch and gelatin. Such biogenic cobalt and cobalt oxide NPs offer more advantages over other physicochemically synthesized methods. In this review, we have summarized the recent literature for the understanding of green synthesis of cobalt and cobalt oxide NPs, their characterization, and various biomedical applications.

Graphical abstract

Keywords: nanotechnology; green synthesis; cobalt nanoparticles; cobalt oxide nanoparticles; biomedical applications of nanoparticles

1 Introduction

Nanotechnology combines various chemical and physical processes to construct nanomaterials, which are less than 100 nm in at least one dimension, and have unique properties [1]. Nanotechnology has applications across different fields, such as nanomedicines, biomaterials, nanoelectronics, environment, imaging, industries, and agriculture [2,3]. In healthcare, it has been widely used for the diagnosis and treatment of diseases, drug delivery, and novel drug formulations [2,4].

Cobalt is a transition metal that has a beneficial effect on human health [5,6]. It constitutes a part of vitamin B12, which is useful in anemia treatment as it provokes the formation of red blood cells [6]. Cobalt has unique magnetic, optical, electrical, and catalytic characteristics that make it suitable for a wide range of applications in the field of nanoelectronics and nanosensors [7,8,9]. Cobalt can exhibit variable oxidation states (Co2+, Co3+, and Co4+), which makes it attractive to be used in several industries [10]. Because of this multivalent state, cobalt has the ability to be present in different spin states in its oxide forms, i.e., low, intermediate, and high [10,11].

Recently, cobalt nanoparticles (CoNPs) have attracted considerable attention because they are more economical than the noble metal nanoparticle (NP) and show different properties, such as electrical and magnetic, due to their large surface area [12,13]. CoNPs have been explored as a therapeutic agent for the treatment of diseases, such as microbial infection, which make them attractive for biomedical applications [14,15]. CoNPs are nontoxic in the body at lower levels, have strong activities against bacteria and fungi at lower concentrations, and have fewer side effects than antibiotics [16,17].

Different types of NPs and their various applications in the area of medicine, textiles, cosmetics, electronics, optics, energy generation, and environmental science have been reported [18,19,20,21,22]. These NPs include silver NPs (AgNPs), iron NPs, CoNPs, copper NPs, gold NPs, silica NPs, platinum NPs, palladium NPs, zinc oxide NPs, magnesium oxide NPs, cerium dioxide NPs, and titanium oxide NPs [18]. Among all NPs, cobalt and cobalt oxide (Co3O4) NPs have been exploited the most because of their unique and wide range of applications [5,6]. Co3O4 is an antiferromagnetic p-type semiconductor with a direct optical band gap of 1.48 and 2.19 eV [23,24]. Co3O4 is a multifunctional material and has many applications such as biomedical applications (antibacterial, antiviral, antifungal, antileishmanial, therapeutic agents, anticancer, and drug delivery), gas sensors, solar selective absorbers, anode materials in lithium-ion batteries, energy storage, pigments and dyes, field emission materials, capacitors, heterogeneous catalysis, magneto-resistive devices, and electronic thin films [25,26,27,28,29] as shown in Figure 1. The oxides of cobalt are abundant in nature, as only the Co3O4 and CoO are stable [30], with Co3O4 possessing the highest stability. In this review, we aim to focus on the biological synthesis, characterization, and biological activities of cobalt and cobalt oxide NPs.

Figure 1 General applications of cobalt and cobalt oxide NPs.
Figure 1

General applications of cobalt and cobalt oxide NPs.

2 Synthesis of NPs

Different approaches can be used for the synthesis of NPs. These approaches are divided into two classes: top-down approach and bottom-up approach. A top-down approach is a destructive approach in which larger molecules are decomposed into smaller ones, and these smaller molecules are then converted into suitable NPs, whereas the bottom-up is a building approach that involves the assembly of atomic size to form nano-size particles [1]. Examples of the top-down approach include chemical etching, laser ablation, mechanical milling, electro-explosion, and sputtering. In these different methods, the bulk materials are first converted into powder form and then into particular NPs. Each synthesis method has its advantages and limitations. The top-down approach has many advantages, such as the production of the desired size and large quantity of nanoparticle, whereas the fabrication of NPs using this method leads to eco-toxicity, high energy consumption and on top of that is expensive and time-consuming [2,3]. The bottom-up approach is further divided into two classes: biological and non-biological approaches. Examples of non-biological approaches include template support synthesis, flame spraying, spinning, laser pyrolysis, atomic condensation, and deposition of chemical vapors. These methods also use toxic chemicals, are expensive and time-consuming, whereas the biological approach uses various biotic resources such as plants, algae, microorganisms, and other biological molecules like starch, egg albumin, and gelatin for the production of different types of NPs. This biological approach is also known as the green approach [2,3,4,5,6,7,8,9,10]. This method is eco-friendly, simple, reliable, biocompatible, and easy for the synthesis of NPs. The classification of various methods of fabrication of NPs is shown in Figure 2. However, in this review, we only focus on the green synthesis of cobalt and cobalt oxide NPs, and their biological applications.

Figure 2 Various methods for the synthesis of cobalt and cobalt oxide NPs.
Figure 2

Various methods for the synthesis of cobalt and cobalt oxide NPs.

3 Green synthesis of cobalt and cobalt oxide NPs (biological methods)

The synthesis of NPs by physical and chemical methods (traditional approaches) has some detrimental effects such as emission of highly expensive and toxic chemicals that carry many threats to the ecosystem, as well as require high energy consumptions, high cost, and time-consuming processes. To overcome these problems, green synthesis of NPs is being implemented. Green-mediated approach emerged as an eco-friendly, biocompatible, and most fascinating, offering more advantages as compared to other traditional approaches [31,32]. In the green-mediated synthesis of NPs, different plants/parts of plants, fruits, bacteria, algae, fungi, and other biological molecules such as starch and egg albumin have been used as a reducing/capping/oxidizing agent [33,34,35]. Different parts of plants, microorganisms, and other biological molecules have been exploited for the fabrication of cobalt and cobalt oxide NPs as shown in Figure 3. These biological resources contain different biomolecules and metabolites that are responsible for the oxidation/reduction, stabilization, and production of particular NPs. Cobalt and cobalt oxide NPs have been synthesized using different methods such as chemical, physical, and biological methods. However, biological approach resulted in less contaminated, safer, cost-effective, and large scale production of NPs [6,31,32].

Figure 3 Use of different plant/parts of plant, microorganism, and other biological molecules for the synthesis of cobalt and cobalt oxide NPs.
Figure 3

Use of different plant/parts of plant, microorganism, and other biological molecules for the synthesis of cobalt and cobalt oxide NPs.

3.1 Green synthesis using plant extracts

In contrast to bacteria, algae, and fungi, plants have been extensively used to synthesize cobalt and cobalt oxide NPs. This is because of their abundance, safe nature, and also the greater stabilization and reduction of plant phytochemicals. This method has been considered as an alternative to complex and costly physicochemical processes because of the following properties: viability, commercial feasibility, eco-friendliness, reliability, no waste generation, and simplicity [36,37]. Different parts of the plant such as leaves, roots, stem, fruits, seeds, latex, inner parts of the plant, shells, and peels have been used to synthesize Co and Co3O4 NPs as shown in Figure 3. The plant extracts have a variety of flavonoids, polysaccharides, amino acids, polyphenols, phenolic acids, ferulic acid, gentisic acid, terpenoids, thymol, tryptophan, and alkaloids, which act as a stabilizing, reducing, and chelating agent as presented in Table 1. These metabolites act as oxygen quenchers, reducing and stabilizing agents, metal chelating agents, and hydrogen donors. The reduction of metal ions by these substances within the plant extracts leads to the formation of respective nanomaterials [38]. Because of a rich source of metabolites, leaf extracts have been widely used for the synthesis of CoNPs. Plant-mediated synthesis of Co and Co3O4 NPs is a simple approach and there is no need for special requirements [6]. The metal salts have been mixed with the whole plant/part of plant extracts, and the reaction completes in a few hours under normal lab conditions [33,34,35,36,37,38].

Table 1

Plant-mediated synthesis of Co and Co3O4 NPs

Plant scientific name/common name Part NPs Characterization Phytoconstituents present in plant Size (nm) Shape References
Conocarpus erectus/buttonwood or button mangrove Leaf extract Cobalt SEM and XRD Tannins, flavonoids, and phenolic acids 20–60 Spherical [31]
Celosia argentea/plumed cockscomb or Silver cock’s comb Whole plant extract Cobalt XRD, SEM, and EDX Flavonoids, tannins, and phenolic acids 27.42 [32]
Punica granatum/pomegranate Peel extract Cobalt oxide XRD, SEM, EDX, AFM, FTIR, and UV Gallic acid, puni87 calagins A and B, ellagic acid, and gallotannins 40–80 Spherical [36]
Ziziphora clinopodioides Lam/kakuti-e kuhi Leaf extract Cobalt UV-vis, XRD, EDS, SEM, TEM, and FTIR Flavonoids, α and β pinen, terpenoids, thymol, piperitenone, sis-isopulegone, pulegone, and cineol 28.19 Crystal [37]
Raphanus sativus var. longipinnatus/Radish Leaf extract Cobalt UV-vis, FTIR, SEM, and EDX Ferulic acid, gentisic acid, raphanusin, erucic acid, sinapate, raphanin, and sulforaphen 80 Spherical [39]
Calotropis gigantea/giant milkweed, crown flower, giant calotrope, swallow-wort Leaf extract Cobalt oxide XRD, UV-vis, SEM, TEM, and EDX Triterpenoids, flavonoids (polyphenols), steroids, cardenolides, and alkaloids 50 Spherical [40]
Hibiscus cannabinus/Deccan hemp and Java jute Leaf extract Cobalt XUV-vis, XRD, SEM, TEM, and FTIR Phytosterols, flavonoids, polyphenols, tannins, steroids, alkaloids, saponins, lignans, essential oils, and glucosides 20.88 Crystalline [41]
Litchi chinensis/litchi fruits Fruits extract Cobalt oxide XRD, SEM, TEM, and FTIR Phenolic acid, flavonoids condensed tannins, luteolin, anthocyanin, and proanthocyanidins. NA Rod like [42]
Sechium edule/perennial climber Fruit extract Cobalt oxide XRD, FTIR, TEM, AFM, SEM, and VSM Ascorbic acid 3.79 Irregular [43]
Helianthus annuus/sunflower Leaf extract Cobalt oxide XRD, TGA, SEM NA NA Plate [44]
Piper nigrum Seeds Cobalt oxide UV-vis, AFM, FTIR NA 30–60 Spongy triangular [45]
Vitis vinifera/common grape vine Whole plant extract Cobalt oxide XRD, FT-IR, Raman, TEM, SAED, EDX, DRS, PL, and VSM Phenolic, stilbenoids, anthocyanin, and acetylated anthocyanin 10–20 Rod shape [46]
Calotropis procera/Sodom apple Latex Cobalt oxide XRD, DSC, TEM, EDX, FTIR, and UV-vis Tryptophan, alkaloids, resins, tannins calotropin, calactin, and calotoxin 10  Spherical [47]
Taraxacum officinale/common dandelion Leaf extract Cobalt oxide UV-vis, FT-IR, SEM, and TEM Flavonoids and phenolic 50–100 Spherical [48]
Mangifera indica/mango Leaf extract Cobalt UV-vis, XRD, FT-IR, and SEM Polyphenolics, flavonoids, and triterpenoids 25–40 Irregular shape [49]
Sageretia thea/Osbeck. Leaf extracts Cobalt oxide XRD, ATR-FTIR, HR-SEM, HR-TEM, SAED, and EDS Friedeline, syringic acid, beta-sitosterol, daucosterol, gluco-syringic acid, and taraxerol 20.03 [50]
Moringa oleifera/drumstick tree, horseradish tree, and ben oil tree or benzolive tree Leaf extract Cobalt oxide HR-TEM, EDS, FTIR, and AXS α-Maltose, adenosine, catechin, chlorogenic acid, rutin, quercetin, kaempferol, caffeic acid, etc. 20–50 Symmetric [51]
Tamarindus indica/tamarind fruit Fruit pulp Cobalt aluminate FTIR, UV-vis, XRD, SEM, and RS Tartaric acid, malic acid, and amino acids 71 Rectangular like [52]
Euphorbia heterophylla/fire plant, painted euphorbia, Japanese poinsettia, desert poinsettia, and wild poinsettia Leaf extract Cobalt oxide FTIR, XRD, Malvern Zetasizer Particle Size Analyzer, TEM, and UV-vis DRS Alkaloid and saponin 69.75 Spherical [53]
Terminalia chebula/black- or chebulic myrobalan Fruit Cobalt oxide ATR-FTIR, XRD, TEM, SEM, and EDS Hydrolysable tannins, gallic acid, chebulic acid, chebulic ellagitannins, and gallate esters 15–25 Spherical [54]
M. oleifera/drumstick Leaf extract Cobalt SEM, FTIR, UV-vis, and EDX Oleic acid, ascorbic acid, dihexadecanoate, octadecenoic acid, methyl ester-hexadecanoic acid, and octadecenamide 168–295 Crystal [55]
Aspalathus linearis/Rooibos Leaf powder Cobalt oxide HR-TEM, EDS, Max solid-state Silicon drift detector, XRD, XPS, FTIR, and Raman spectroscopy Phenolic compounds, aspalalinin, flavones, and flavonols 3.6 Quasi-spherical [56]
Manihtot esculenta Crantz/cassava Whole extract Cobalt oxide SEM, EDS, TEM, FT-IR, XRD, VSM, TGA, and EDX Malonaldehyde, superoxide dismutase, reduced glutathione, and catalase N/A Prism like-anchored octahedron [57]
Zingiber officinale/ginger Whole plant Cobalt XRD, SEM, FTIR, VSM, and EDS Gingerol, zingerone, shagaols, paradole, and starch 20–50 Crystal [58]
Canna indica/Indian shot, African arrowroot, edible canna Leaf extract Bimetallic cobalt UV-vis, TEM, EDX, and Thermo Electron LED Glycosides, alkaloids, and terpenoids 450–550 Polydispersed [59]
S. edule/chayote Fruit extract Bimetallic cobalt AAS, SEM, SAED, TEM, XRD, and EPR Trans-cinnamic acid, phenylacetic acid, trilinolenin, etc. 47.3 Prismoidal [60]
Cinnamomum verum/true cinnamon tree or Ceylon cinnamon tree Bark Cobalt aluminate MCM, XRD, SEM, TEM, XPS, IR, and UV-vis Polysaccharides, polyphenols, flavonoids, and amino acids 50–60 Polyhedral [61]
Camellia sinensis/tea plant, tea shrub, and tea tree Leaf extract Cobalt oxide XRD, FESEM, EDX, HR-TEM, PL, FTIR, and UV-visible Catechins, alkaloids, flavonoids, proteins, enzymes, vitamins, carbohydrates, polyphenols, lipids, and minerals 39.13 Quasi-rectangular [62]
Populus ciliata/safaida Leaf extract Cobalt oxide FTIR, TEM, SEM, and XRD Alcohol-benzene, lignin, holocellulose, and alphacellulose 15–35 Square shape [63]
Tamarindus indica/Indian tamarind Fruit extract Cobalt aluminate FTIR, UV-vis, XRD, SEM, and TEM Tartaric acid, malic and citric acid, potassium ditartrate, amino acids, and vitamin B 71.3 Cubic spinel [64]
S. thea/Osbeck. Leaf extract Cobalt oxide XRD, TEM, SEM, SAED, and EDS Acids/base 20.03 Cubic [65]
Cirsium vulgare Leaf extract Cobalt oxide XRD, SEM, and TEM NA 20 [66]
Trigonella foenumgraceum/fenugreek Leaf extract Cobalt oxide FTIR, XPS, XRD, EDS, UV-vis, and TEM Flavonoids, polyphenols, and different glycosides 13.2 Quasi-spherical [67]
Withania coagulans Whole plant extract Cobalt oxide UV-vis and XRD Withanolide, withaferin, and withacoagin NA Cube shape [68]
Chromolaena odorata Leaf extract Cobalt UV-vis, XRD, FT-IR, and SEM NA 20–49 Irregular, cubic, and hexagonal shapes [69]
Catharanthus roseus/periwinkle Whole plant extract Cobalt XRD, FESEM, and EDX Alkaloids, tannins, flavonoids, polyphenols, and carbohydrates 27.08 Spherical shape [70]
Sesbania sesban Whole extract Cobalt oxide HR-TEM, EDAX, and XRD NA 15–30 Spherical [71]

Abbreviations: NPs, nanoparticles; NA, not available; SAED, selected area electron diffraction; UV-vis, ultraviolet visible spectroscopy; XPS, X-ray photoelectron spectroscopy; TEM, transmission electron microscopy; XRD, X-ray diffraction; AFM, atomic force microscopy; HR-SEM, high-resolution scanning electron microscopy; HR-TEM, high-resolution transmission electron microscopy; EDX, energy-dispersive X-ray(spectroscopy); FTIR, Fourier-transform infrared spectroscopy; NA, not available; UV-DRS, ultraviolet differential reflectance spectroscopy; TGA, thermo gravimetric analysis; VSM, vibrating sample magnetometer; PL, photoluminescence spectroscopy; PDXL, integrated X-ray powder diffraction software; EDS, energy-dispersive X-ray spectroscopy.

Raphanus sativus var. longipinnatus leaf extract was used to fabricate CoNPs with a spherical structure that represents the presence of ferulic acid, gentisic acid, raphanusin, erucic acid, sinapate, and sulforaphen. The green-synthesized NPs were characterized by UV-visible spectroscopy (UV-vis), X-ray diffraction (XRD), and scanning electron microscopy-energy-dispersive X-ray (spectroscopy) (SEM-EDX). These CoNPs showed potential antibacterial activities and also showed promising cytotoxic activities against the HeLa cancer cell lines in vitro [39]. Co3O4 NPs were synthesized having spherical morphologies with a diameter size of 50–60 nm, using Calotropis gigantea leaf extracts that indicate the presence of triterpenoids, flavonoids (polyphenols), steroids, cardenolides, and alkaloids [40]. Hibiscus cannabinus leaf extract was used to synthesize crystalline CoNPs having a diameter of 20.8 nm. These CoNPs were characterized by UV-vis, XRD, and Fourier-transform infrared spectroscopy (FTIR). Authors reported that the green-synthesized NPs have strong activities against Bacillus subtilis and Escherichia coli [41]. Onwudiwe et al. (2020) reported the bio-mediated synthesis of Co3O4 NPs using the fruit extract of Litchi chinensis. The characterizations of synthesized NPs were confirmed by XRD, SEM, transmission electron microscopy (TEM), and FTIR. SEM analysis revealed that the bioinspired NPs had elongate rod-like morphology. FTIR analysis was also carried out to detect the functional group of various phytochemicals that are involved in the oxidation/reduction and hence the formation of cobalt oxide NPs. The FTIR analysis confirmed the presence of phenolic and carboxylic functional groups, indicating that these groups are responsible for the formation of cobalt oxide NPs [42]. Sechium edule and Helianthus annuus fruits’ extracts [34,44] and Piper nigrum seeds [45] have also been reported for the synthesis of Co3O4 NPs. Vitis vinifera whole plant extracts were used for the synthesis of Co3O4 NPs having a pure single crystalline structure with a size of 10–20 nm in diameter. The TEM and FTIR analysis indicated that the plant extracts play an important role in the stabilization and reduction of nanorods via different types of organic compounds present in the plant extracts [46]. Latex derived from Calotropis procera was used to synthesize Co3O4 NPs with spherical morphologies and average size of 10 nm diameter. These NPs showed only a low toxicity at a very high concentration, proving that they are safe and may be used for different applications in various fields including the field of medicines [47]. Other than aforementioned, different parts of various plants, used for the synthesis of Co and Co3O4 NPs are shown in Table 1 and Figure 3.

3.2 Synthesis of Co and Co3O4 NPs using microorganisms

3.2.1 Bacteria-mediated synthesis

Similar to other synthesis routes such as those of plants and other microorganisms, bacteria also have an intrinsic ability to synthesize NPs of different sizes and morphologies. To date, different types of bacterial strains have been used to synthesize Co and Co3O4 NPs [33,72,74]. This approach also has some challenges compared to other methods that are yet to be solved, like the synthesis of complex materials with the desired phase, a full understanding of the synthesis mechanism at the molecular level to achieve better control over shape and size, and scaling up in order to obtain large amounts of nanomaterials [73]. Chemical methods are already advanced to provide greater control on the shape and size of nanomaterials, but this approach is eco-friendly and limits the drawbacks of the chemical synthesis [73]. However, lengthy procedures and contamination of cultures are the limitations of this approach. Different bacterial species have been used for the synthesis of cobalt and cobalt oxide NPs.

A gram-positive bacterium Bacillus thuringiensis was used to synthesize Co NPs having face-cubic morphology with an average size of 85.3 nm diameter. These green-synthesized NPs were investigated against malarial and dengue vectors (Aedes aegypti and Anopheles subpictus) and showed potential activities against these vectors [75]. Co3O4 NPs synthesized using bacterial strains Micrococcus lylae and B. subtilis have globular and rod shape morphology, respectively [74]. Gram-negative bacterium Proteus mirabilis was used to synthesize CoNPs with an average size of 57 nm and quasi-spherical morphology. The authors evaluated the antibacterial activity of these NPs, and the result showed that these NPs were promising antimicrobial potential against Salmonella typhi, E. coli, Clostridium perfringens, Staphylococcus aureus, and Bacillus cereus [76]. Table 2 provides some examples of bacterial-mediated synthesized Co and Co3O4 NPs.

Table 2

Bacterial-mediated synthesis of Co and Co3O4 NPs

Bacterial strain Gram+/Gram− NPs Characterization Size (nm) Shape References
Bacillus pasteurii Gram+ Cobalt oxide XRD, SEM, FE SEM, TEM, and HR-TEM 10–31 Irregular [33]
Bacillus subtilis Gram+ Cobalt oxide XRD, SEM, FE SEM, TEM, and HR-TEM 6.6 Hollow rod [72]
Brevibacterium casei Gram+ Cobalt oxide XRD, SEM, FE SEM, TEM, and HR-TEM 6 Quasi-spherical [73]
Micrococcus lylae Gram+ Cobalt oxide XRD, SEM, FE SEM, TEM, and HR-TEM 8 Flower like [77]
B. subtilis Gram+ Cobalt oxide FESE, M ELS-Z2, FESEM, XPS, and EPMA 3–5 Rods [78]
M. lylae Gram+ Cobalt oxide XRD, TGA, FE-SEM, TEM, EDS, SAED, and HAADF-STEM 40 Spherical [79]
M. lylae Gram+ Cobalt Zetasizer Nano system and FESEM 356 ± 55 Globular [74]
B. subtilis Gram+ Cobalt Zetasizer Nano system and FESEM NA Rod shape [74]
Escherichia coli Gram− Cobalt Zetasizer Nano system and FESEM 473 ± 54 Rod shape [74]
Paracoccus sp. Gram− Cobalt Zetasizer Nano system and FESEM NA Biconcave [74]
Haloarcula vallismortis Gram− Cobalt Zetasizer Nano system and FESEM NA Globular [74]
Proteus mirabilis Gram− Combine Cobalt UV-vis, EDX, XRD, TEM, DLS, and PDI 57 Quasi-spherical [76]
Bacillus thuringiensis Gram+ Cobalt XRD, TEM, FESEM, FTIR, and EDX 85.3 Face-cubic [75]

Abbreviations: NPs, nanoparticles; NA, not available; SAED, selected area electron Diffraction; UV-vis, Ultraviolet visible spectroscopy; XPS, X-ray photoelectron spectroscopy; TEM, transmission electron microscopy; XRD, X-ray diffraction; HR-TEM, high-resolution transmission electron microscopy; EDX, energy-dispersive X-ray(spectroscopy); FTIR, Fourier-transform infrared spectroscopy; TGA, thermo gravimetric analysis; ATR-FTIR, attenuated total reflectance-Fourier transform infrared spectroscopy; FESEM, field emission scanning electron microscopy; EPMA, electron probe microanalyzer; HAAD-STEM, high-angle annular dark field scanning TEM; EDS, energy-dispersive X-ray spectroscopy.

3.2.2 Fungi-mediated synthesis of Co3O4 NPs

The fungi-mediated approach exhibits unique advantages, as the growth process of fungi is easy to handle and isolate, with the large amount of biomass and high yield of proteins [34]. The entophytic fungi also secrete large amounts of bioactive substances that are necessary for the synthesis of NPs in the presence of precursor substance [34,80]. During the fabrication of NPs from the precursor solution, biomass (fungi) along with the supernatant act as a reduction medium [34,81].

Using fungi, NPs can be synthesized by two pathways: intracellular and extracellular synthesis. The extracellular approach is more commonly used because of the facile separation, high mass harvesting, and easy culturing, which consequently leads to the scaling up of the process at the commercial level [82]. Fungi can also tolerate agitation, flow pressure, and other conditions in the bioreactor for commercial production. Filamentous fungi are highly resistant toward metals as compared to bacteria [83,84]. Different fungal and yeast strains have been used to synthesize cobalt oxide NPs. Aspergillus nidulans was used to synthesize spherical shape Co3O4 NPs with an average size of 20.29 nm diameter [34]. Some examples of yeast and fungi-mediated synthesis of Co3O4 NPs are presented in Table 3.

Table 3

Fungal-mediated synthesis of Co and Co3O4 NPs

Fungal species used NPs Characterization Size (nm) Shape References
Aspergillus nidulans Cobalt oxide XRD, TEM, FTIR, and EDX 20.29 Spherical [34]
Aspergillus brasiliensis Cobalt oxide DLS, EDX, XRD, FT-IR, HR-TEM, and FESEM 20–27 Quasi-spherical [83]
Nothapodytes foetida Cobalt oxide UV-vis N/A H/A [85]
Yeast Cobalt oxide SEM, XRD, and FT-IR 24 Hollow spheres [86]

Abbreviations: NPs, nanoparticles; NA, not available; UV-vis, ultraviolet visible spectroscopy; XPS, X-ray photoelectron spectroscopy; TEM, transmission electron microscopy; XRD, X-ray diffraction; HR-TEM, high-resolution transmission electron microscopy; EDX, energy-dispersive X-ray(spectroscopy); FTIR, Fourier-transform infrared spectroscopy; VSM, vibrating-sample magnetometer; FESEM, field emission scanning electron microscopy.

3.3 Algal-mediated approach for the synthesis

Algae are aquatic microorganisms that are used to a great extent for the synthesis of NPs. Algae are also called bionanofactories because they fabricate nanomaterials with high stability, are easy to handle, and do not need cell maintenance [87]. Algae are the key origin of bioactive metabolites that are involved in the fabrication of NPs [88,89]. They contain many bioactive metabolites such as proteins, polysaccharides, and various types of other phytochemicals that are comprised of amino, hydroxyl, and carboxyl functional groups, which are responsible for the fabrication of NPs [87,90]. Algae differ in size and can vary from microalgae to macroalgae [87,88,89,90]. A green-type macroalgae Enteromorpha flexuosa was used to synthesize cobalt–ferrite NPs with an average size of 5–15 nm. These bioinspired cobalt ferrite NPs were characterized by various advanced techniques such as XRD, SEM, TEM, energy-dispersive X-ray spectroscopy (EDS), and XPS [91]. Similarly, cobalt tungstate (CoWO4) NPs synthesized from red seaweeds (Rhodophyta) using agar-agar have also been reported [92].

3.4 Biological product-mediated synthesis of Co and Co3O4 NPs

The plants and microorganisms are widely used for the fabrication of NPs. Besides these, the biological derivatives are used to synthesize NPs as well. They also play a significant role in the stabilization and reduction of nanomaterials [93]. Co3O4 nanocrystals were synthesized from freshly extracted ovalbumin with 8–17 nm diameter confirmed by EPR [94]. Sun et al. (2019) also reported the synthesis of Co3O4 NPs using egg-albumin. Hosein et al. (2004) reported the synthesis of Co3O4 NPs with a uniform shape and size using ferritin [95]. Starch has also been exploited for the synthesis of carbon-encapsulated Co NPs with an average size of 20–35 nm diameter and confirmed by the nanostructure by SEM, TEM, and XRD [96]. Similarly, peptide TLVNN (threonine–leucine–valine–asparagine–asparagine) was also used as a capping agent for in situ syntheses of CoNPs for bioapplications [97].

4 Biological activities of Co and Co3O4 NPs

4.1 Antibacterial activity

Currently, throughout the globe, the emergence of bacterial resistance to the available antibiotics is a major health concern. Therefore, there is a need for the antibiotic agent that can kill pathogenic bacteria which show resistance to the available drugs [98]. The NPs have small size with high surface area compared to the bigger molecules and therefore possess strong antibacterial activities. The NPs have dose-dependent membrane permeation and inhibit the synthesis of bacterial proteins by disturbing the cell membrane [32,99]. Different metallic NPs such as gold, iron, silver, and metal oxide NPs such as iron oxide, cobalt oxide, and copper oxide showed significant antibacterial activities. The AgNPs are the main interest not only in biomedical industries but also in food industries because of its potential antimicrobial behavior [114]. Cobalt and cobalt oxide NPs also possess potential antibacterial activity. Varaprasad et al. (2017) measured the antibacterial activity of biogenic CoNPs against human pathogenic bacteria, and the results concluded that CoNPs have strong antibacterial activities compared to standard antibiotic drug ciprofloxacin [100]. Eltarahony et al. (2018) reported the green synthesis of combined CoNPs using gram-negative bacteria P. mirabilis. The characterization of NPs was confirmed by UV-vis, EDX, XRD, TEM, dynamic light scattering (DLS), and poly dispersity index (PDI). The antibacterial activity was observed using a well diffusion assay against S. typhi, E. coli, C. perfringens, S. aureus, and Enterococcus faecalis [76]. The result showed that the NPs have promising biocide efficiency against these bacteria [76]. Omran et al. (2019) synthesized quasi-spherical shape cobalt oxide NPs with an average size of 20–27 nm diameter using a fungal specie Aspergillus brasiliensis. The first-time mycosynthesized cobalt oxide NPs showed considerable activity against different bacteria [83]. Biogenic synthesis of CoNPs using Celosia argentea whole plant extract has been reported and studied for their antibacterial activities using the disk diffusion method. The synthesized NPs showed remarkable antibacterial activities against B. subtilis and E. coli [32]. Green-mediated cobalt oxide NPs have been synthesized using Hibiscus rosa-sinensis flower extract and their antibacterial activity was measured. These green-synthesized NPs showed promising activities against E. coli, Streptococcus mutans, S. aureus, and Klebsiella pneumonia [101]. Mainly two aspects have been suggested. First, in cobalt oxide NPs, the different positive states of cobalt ions, i.e., Co2+ and Co3+ interact with the parts of the bacterial cell that have a negative charge and cause the death of the bacterial cell. Second, there may be the excitement of electrons on the surface of cobalt oxide because of light irradiation in the conduction and valence band. In the conduction band, there is the formation of superoxide radical anion because of the reaction of excited electrons and oxygen molecules. Finally, the formation of hydrogen peroxide, which is a strong oxidant, occurs. On the surface of NPs, the reaction of water and superoxide radical anion destroys the bacterial cell. Therefore, Cobalt oxide nanoparticles can be a potent antibacterial agent at a minimal level of concentration [6,102]. The antibacterial activities of cobalt and cobalt oxide NPs synthesized from different green routes are presented in Table 4.

Table 4

Antibacterial activities of green-synthesized cobalt and cobalt oxide NPs

Biological entity NPs Test microorganisms Method References
Celosia argentea Cobalt Bacillus subtilis and Escherichia coli Disk diffusion [32]
Ziziphora clinopodioides Lam Cobalt Salmonella typhimurium, E. coli, Streptococcus pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, and B. subtilis Disk diffusion [37]
Raphanus sativus var. longipinnatus Cobalt Pseudomonas putida and Klebsiella pneumonia Disk diffusion [39]
Hibiscus cannabinus Cobalt B. subtilis and E. coli Agar well diffusion [41]
Vitis vinifera Cobalt oxide P. aeruginosa, E. coli, S. aureus, and B. subtilis Disk diffusion [46]
Calotropis procera Cobalt oxide E. coli, Pseudomonas sp., Alcaligenes sp., and Enterococcus sp. Disc diffusion [47]
Moringa oleifera Cobalt E. coli and S. aureus Agar well diffusion [51]
Sechium edule Bimetallic cobalt B. subtilis and E. coli Disk diffusion [60]
Populus ciliata Cobalt oxide Bacillus licheniformis, B. subtilis, K. pneumonia, and E. coli Well diffusion [63]
Sageretia thea Cobalt oxide P. aeruginosa, E. coli, K. pneumonia, Staphylococcus epidermis, S. aureus, and B. subtilis Disc diffusion [65]
Chromolaena odorata Cobalt E. coli, K. pneumonia, S. aureus, and Streptococcus pyogenes Agar well diffusion [69]
Catharanthus roseus/Periwinkle Cobalt B. subtilis and E. coli Disc diffusion [70]
Sesbania sesban Cobalt oxide S. aureus Disk diffusion [71]
Proteus mirabilis Cobalt P. aeruginosa, Salmonella typhi, E. coli, Clostridium perfringens, Enterococcus faecalis, Bacillus cereus, and S. aureus Well diffusion [76]
Aspergillus brasiliensis Cobalt oxide B. subtilis, S. aureus, P. aeruginosa, and E. coli Agar well diffusion [83]

Abbreviation: NPs, nanoparticles.

4.2 Antifungal activity

The resistance of bacteria and fungi to the available antibiotics and drugs is at an alarming rate. Therefore, there is a need for strong antifungal agents that can destroy fungi that are resistant to the drugs available [19]. Cobalt and cobalt oxide NPs have various biomedical applications because of different properties including antifungal property. Hou et al. (2020) measured the antifungal properties of green-synthesized CoNPs, and the result showed that the CoNPs have strong antifungal activities against Candida krusei, Candida guilliermondii, Candida glabrata, and Candida albicans [37]. Similarly, cobalt oxide NPs synthesis using flower extract of H. rosa-sinensis and their antifungal activities has been reported. The result showed that the synthesized NPs have strong activities against Aspergillus flavus and A. niger [62].

4.3 Larvicidal activities of CoNPs

For tropical and subtropical countries, the vector and vector-borne diseases have become a big trouble for public health [103]. For the human vector-borne infectious disease, the microorganisms (parasite, bacterium, or virus) and the vectors (mosquito, fly, or tick) are the crucial elements [104]. Mosquitos are the vector of infectious diseases such as dengue, malaria, fever, and yellow fever [104]. The mosquitoes affect humans as well as domestic animals throughout the globe. The biocontrol method is being considered because of high resistance to the chemical insecticides and no new approaches to control the mosquitos. In this approach, different microbes, e.g., B. thuringiensis, have been used in regards to their toxicity to the target vector [75,105,106].

A. subpictus and A. aegypti are the vectors that cause malaria and dengue, respectively, and are the main species of medical interest. In more than 100 countries, about 2.5 billion people are at risk of infection with dengue. Fifty million people are affected worldwide with more than 24,000 deaths per year. There is a need for development of new agents to control these vectors [75]. CoNPs have also been tested against malarial A. subpictus and A. aegypti. Marimuthu et al. (2013) tested the bacterial-mediated synthesized CoNPs using B. thuringiensis against malarial and dengue vectors in vitro. The results showed that the green-synthesized CoNPs have promising activities that exceed those of biocontrol agent (B. thuringiensis) against these vectors [75]. Therefore, it may possible to use the CoNPs in drug formulation against these parasites.

4.4 Antileishmanial activity

The World Health Organization considered the leishmaniasis as one of the uncontrolled, emerging, and neglected diseases with the second-highest prevalence rate, with malaria placing itself at the topmost among the parasitic diseases [107]. Leishmaniasis is caused by leishmania parasites that exist in two forms, promastigote (motile) and amastigote (non-motile) [108]. Leishmaniasis occurs mainly in two clinical forms: visceral leishmaniasis (also called kala-azar), which is the most severe form and - if left untreated - may lead to death, and cutaneous leishmaniasis. It is predicted that about 0.5 million cases of visceral leishmaniasis and 1.5 million cases of cutaneous leishmaniasis occur throughout the globe per year [109]. This deadly disease is endemic in 98 countries of the world. Currently, no vaccines are available against leishmaniasis. The only option available are the treatment drugs and none of the available drugs is ideal because of their cost, duration of therapy, severe side effects, high toxicity, and - most importantly - the resistance of leishmania parasites to the available treatment [107]. Therefore, there is an immediate need to develop an effective antileishmanial approach to combat this deadly infection.

Talha et al. (2017) synthesized cobalt oxide NPs using the extract of Sageretia thea (Osbeck.), a medicinal plant. The characterizations were confirmed by XRD, FTIR, EDS, selected area electron diffraction, high-resolution scanning electron microscopy, and high-resolution transmission electron microscopy. For the first time the antileishmanial activity of the green-synthesized NPs was evaluated using MTT cytotoxic assay. The results showed that the antileishmanial response was dose dependent, and the amastigote parasites were most susceptible as compared to the promastigote. Therefore, cobalt oxide NPs may be one of the possible options in nanomedicine to treat leishmania at any stage of the life cycle [50].

4.5 Antioxidant activity

Oxidative metabolism is a key process for the survival of cells. However, this process has some side effects as they produce free radicals and reactive oxygen species. When these free radicals are produced in the body in the excess amount they can inundate the enzymes such as catalases, peroxidase, and superoxide dismutase and lead to lethal cellular effects by oxidizing cellular proteins, membrane lipids, DNA enzymes, and influence signaling pathways of the cell leading to termination of cellular respiration [110]. Oxidation affects food as well, which is one of the main causes of chemical spoilage that affects flavor, texture, nutritional value, and safety of food. Different types of natural and synthetic antioxidants are available to limit the side effects of oxidation [110,111].

NPs also have strong antioxidant activities. Plant-mediated cobalt oxide NPs having cubic shape morphologies with an average size of 20.03 nm diameter have been prepared using the leaf extract of S. thea. The antioxidant assays, free radical scavenging, total antioxidant capacity, and total reducing power have been evaluated. The biogenic cobalt oxide NPs showed superior radical scavenging potential and an average total antioxidant capacity and total reducing power [50]. Shahzadi et al. (2019) also observed radical scavenging activity of bioinspired CoNPs and reported that the scavenging power and antioxidant activity are dose dependent: the increase of activity leads to the increase in the concentration of CoNPs [32]. CoNPs using the leaf extract of Ziziphora clinopodioides Lam has been synthesized and the antioxidant activities were evaluated. The green-synthesized NPs showed impressive results and have good DPPH free radical scavenging activity [37]. Similarly, DPPH radical scavenging activity of cobalt oxide NPs synthesized from the Sesbania sesban extract has been reported to have minimum activities compared to silver and copper oxide NPs [71].

4.6 Cytotoxic activity

Cytotoxicity assay is a test for the characterization and evaluation of potentially harmful and toxic effects of biomolecules or any other materials on the living organisms/cell cultures. Various types of molecules, plant extracts, and NPs have been used to check the cytotoxic effect [112]. The green-synthesized CoNPs were used in different concentrations to investigate and determine the cytotoxicity of human umbilical vein endothelial cells (HUVECs) in vitro. The cells treated with various concentrations of CoNPs were examined by the MTT test for 48 h. The absorbance rate was determined at 570 nm, which indicated good viability on (HUVECs) cell lines even up to 1,000 mg/mL of CoNPs, and the absence of such type of toxicity of CoNPs has many safe applications in nanomedicines [37]. Padigya et al. (2016) observed the cytotoxic effect of the biogenic CoNPs on HeLa cell lines. They reported that CoNPs showed potential cytotoxic effects against HeLa cancer cell lines [39]. The green-synthesized cobalt oxide NPs were also investigated for cytotoxicity through brine shrimp cytotoxicity assay. Cytotoxicity of the Co3O4 NPs was confirmed by their dose-dependent response, whereas the median lethal concentration was calculated as 19.18 μg/mL [50].

4.7 Hemolytic activities

Hemolysis is the release of hemoglobin in the blood because of the disruption of erythrocyte membranes that may lead to jaundice or anemia. That is why it is very important to check the hemolytic activity of any newly synthesized preparate that can be used for pharmacological purposes [113]. Shahzadi et al. (2019) evaluated the hemolytic activity of green-synthesized CoNPs using the plant extract of C. argentea. The results showed that the biosynthesized CoNPs have less hemolytic activity (2.95%) compared to positive control triton-X-100 which has 95.25% toxicity, whereas the negative taken has 1.02% toxicity [32]. Zaib et al. (2019) fabricated CoNPs using the Catharanthus roseus extract and evaluated their hemolytic activities. They reported that the hemolysis rate of CoNPs is approximately 1.53%, with the negative and positive control rates of 1.02% and 95.28%, respectively [70]. Therefore, CoNPs can be used in drug formation because of their safety, cost-effectiveness, and nontoxic nature. Cobalt oxide NPs were prepared using S. thea extract and evaluated in regards to their biocompatibility and various biological applications. The result presented that the median lethal dose concentration was observed as >58.55 µg/mL and 200 µg/mL for macrophages and RBCs, respectively [50]. For that reason the biosynthesized cobalt oxide NPs might be used at low concentrations for drug formulations.

4.8 Other biological applications

Apart from antimicrobial, antioxidant, antileishmanial, cytotoxic, hemolytic, and larvicidal activities, Co and Co3O4 NPs have various biological and medical applications. After cardiovascular diseases, cancer is the second main cause of human dysphoria [19]. CoNPs showed promising anticancer activities. Kgosiemang et al. (2020) synthesized cobalt oxide NPs using the Euphorbia tirucalli extract and investigated the anti-proliferative activity using MTT assay against MCF-7 breast cancer cell lines. The result showed that the biosynthesized cobalt oxide NPs exhibit promising activities against MCF-7 breast cancer cell lines [53]. The cutaneous wound healing potential of green-synthesized CoNPs has been investigated and it was reported that the ointment of CoNPs has great potential in cutaneous wound healing [37]. The catalytic activity, enzyme inhibition, antidiabetic activity, and anticholinergic activity of biogenic cobalt and cobalt oxide NPs have been reported [37,50].

5 Conclusion

The green-synthesized cobalt and cobalt oxide NPs have various biological and biomedical applications. Traditionally, NPs are synthesized by either physical or chemical methods, which leads not only to environmental toxicity but also to costly and energy-intensive labor. Cobalt and cobalt oxide NPs are synthesized by a green route using the extracts of different plants/parts of plants, microorganisms, and other biological molecules such as gelatin, oleic acid, and starch. The biomediated cobalt and cobalt oxide NPs are environmentally friendly, facile in terms of synthesis, cost effective, and biocompatible.

  1. Funding: The authors state no funding involved.

  2. Author contributions: A. W. and M. A. – conceptualization and original draft preparation; A. W., A. A., A. B., M. D., S. A., and A. U. K. – review and editing. All the authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

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Received: 2020-09-14
Revised: 2020-10-20
Accepted: 2020-11-17
Published Online: 2021-01-20

© 2021 Abdul Waris et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/biol-2021-0003
Keywords for this article
nanotechnology; green synthesis; cobalt nanoparticles; cobalt oxide nanoparticles; biomedical applications of nanoparticles
Creative Commons
BY 4.0

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  10. Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
  11. ABCB1 polymorphism in clopidogrel-treated Montenegrin patients
  12. Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats
  13. miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2
  14. Verification of neuroprotective effects of alpha-lipoic acid on chronic neuropathic pain in a chronic constriction injury rat model
  15. Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis
  16. Knockdown of TUG1 rescues cardiomyocyte hypertrophy through targeting the miR-497/MEF2C axis
  17. MiR-146b-3p protects against AR42J cell injury in cerulein-induced acute pancreatitis model through targeting Anxa2
  18. miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer
  19. Diabetes and COVID-19
  20. Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor
  21. TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation
  22. circTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis
  23. microRNA-9-5p protects liver sinusoidal endothelial cell against oxygen glucose deprivation/reperfusion injury
  24. Long noncoding RNA TUG1 regulates degradation of chondrocyte extracellular matrix via miR-320c/MMP-13 axis in osteoarthritis
  25. Duodenal adenocarcinoma with skin metastasis as initial manifestation: A case report
  26. Effects of Loofah cylindrica extract on learning and memory ability, brain tissue morphology, and immune function of aging mice
  27. Recombinant Bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways
  28. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
  29. Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders
  30. Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis
  31. Vitamin D deficiency and cardiovascular risk in type 2 diabetes population
  32. Circ_0013359 facilitates the tumorigenicity of melanoma by regulating miR-136-5p/RAB9A axis
  33. Mechanisms of circular RNA circ_0066147 on pancreatic cancer progression
  34. lncRNA myocardial infarction-associated transcript (MIAT) knockdown alleviates LPS-induced chondrocytes inflammatory injury via regulating miR-488-3p/sex determining region Y-related HMG-box 11 (SOX11) axis
  35. Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis
  36. Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis
  37. Potential prognostic markers and significant lncRNA–mRNA co-expression pairs in laryngeal squamous cell carcinoma
  38. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development
  39. ADHFE1 is a correlative factor of patient survival in cancer
  40. The association of transcription factor Prox1 with the proliferation, migration, and invasion of lung cancer
  41. Is there a relationship between the prevalence of autoimmune thyroid disease and diabetic kidney disease?
  42. Immunoregulatory function of Dictyophora echinovolvata spore polysaccharides in immunocompromised mice induced by cyclophosphamide
  43. T cell epitopes of SARS-CoV-2 spike protein and conserved surface protein of Plasmodium malariae share sequence homology
  44. Anti-obesity effect and mechanism of mesenchymal stem cells influence on obese mice
  45. Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis
  46. Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress
  47. Prognostic value of the neutrophil-to-lymphocyte ratio in acute organophosphorus pesticide poisoning
  48. Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities
  49. Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis
  50. Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report
  51. Effects of miR-185-5p on replication of hepatitis C virus
  52. Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
  53. Primary localized cutaneous nodular amyloidosis presenting as lymphatic malformation: A case report
  54. Multimodal magnetic resonance imaging analysis in the characteristics of Wilson’s disease: A case report and literature review
  55. Therapeutic potential of anticoagulant therapy in association with cytokine storm inhibition in severe cases of COVID-19: A case report
  56. Neoadjuvant immunotherapy combined with chemotherapy for locally advanced squamous cell lung carcinoma: A case report and literature review
  57. Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
  58. Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
  59. Invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia manifesting as a collision breast tumor: A case report and literature review
  60. Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes
  61. CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression
  62. WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway
  63. Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis
  64. Curcumin suppresses the progression of gastric cancer by regulating circ_0056618/miR-194-5p axis
  65. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway
  66. lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis
  67. A two-microRNA signature predicts the progression of male thyroid cancer
  68. Isolation of microglia from retinas of chronic ocular hypertensive rats
  69. Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study
  70. Calcineurin Aβ gene knockdown inhibits transient outward potassium current ion channel remodeling in hypertrophic ventricular myocyte
  71. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
  72. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer
  73. circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells
  74. Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function
  75. Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway
  76. Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso
  77. Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock
  78. Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway
  79. Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs
  80. Downregulation of STOX1 is a novel prognostic biomarker for glioma patients
  81. miR-378a-3p regulates glioma cell chemosensitivity to cisplatin through IGF1R
  82. The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats
  83. TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ
  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
  85. Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women
  86. Small cell neuroendocrine carcinoma expressing alpha fetoprotein in the endometrium
  87. Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
  88. Molecular characterization and phylogenetic studies of Echinococcus granulosus and Taenia multiceps coenurus cysts in slaughtered sheep in Saudi Arabia
  89. ITGB5 mutation discovered in a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome
  90. ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting
  91. Facilitation of mouse skin-derived precursor growth and yield by optimizing plating density
  92. 3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model
  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
  94. Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B
  95. Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells
  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
  97. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
  98. Bioengineering and Biotechnology
  99. Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review
  100. Agriculture
  101. Effects of inorganic and organic selenium sources on the growth performance of broilers in China: A meta-analysis
  102. Crop-livestock integration practices, knowledge, and attitudes among smallholder farmers: Hedging against climate change-induced shocks in semi-arid Zimbabwe
  103. Food Science and Nutrition
  104. Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce
  105. Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China
  106. Diversity of microbiota in Slovak summer ewes’ cheese “Bryndza”
  107. Comparison between voltammetric detection methods for abalone-flavoring liquid
  108. Composition of low-molecular-weight glutenin subunits in common wheat (Triticum aestivum L.) and their effects on the rheological properties of dough
  109. Application of culture, PCR, and PacBio sequencing for determination of microbial composition of milk from subclinical mastitis dairy cows of smallholder farms
  110. Investigating microplastics and potentially toxic elements contamination in canned Tuna, Salmon, and Sardine fishes from Taif markets, KSA
  111. From bench to bar side: Evaluating the red wine storage lesion
  112. Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women
  113. Plant Sciences
  114. Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
  115. Comparative analysis of the SPL gene family in five Rosaceae species: Fragaria vesca, Malus domestica, Prunus persica, Rubus occidentalis, and Pyrus pyrifolia
  116. Identification of leaf rust resistance genes Lr34 and Lr46 in common wheat (Triticum aestivum L. ssp. aestivum) lines of different origin using multiplex PCR
  117. Investigation of bioactivities of Taxus chinensis, Taxus cuspidata, and Taxus × media by gas chromatography-mass spectrometry
  118. Morphological structures and histochemistry of roots and shoots in Myricaria laxiflora (Tamaricaceae)
  119. Transcriptome analysis of resistance mechanism to potato wart disease
  120. In silico analysis of glycosyltransferase 2 family genes in duckweed (Spirodela polyrhiza) and its role in salt stress tolerance
  121. Comparative study on growth traits and ions regulation of zoysiagrasses under varied salinity treatments
  122. Role of MS1 homolog Ntms1 gene of tobacco infertility
  123. Biological characteristics and fungicide sensitivity of Pyricularia variabilis
  124. In silico/computational analysis of mevalonate pyrophosphate decarboxylase gene families in Campanulids
  125. Identification of novel drought-responsive miRNA regulatory network of drought stress response in common vetch (Vicia sativa)
  126. How photoautotrophy, photomixotrophy, and ventilation affect the stomata and fluorescence emission of pistachios rootstock?
  127. Apoplastic histochemical features of plant root walls that may facilitate ion uptake and retention
  128. Ecology and Environmental Sciences
  129. The impact of sewage sludge on the fungal communities in the rhizosphere and roots of barley and on barley yield
  130. Domestication of wild animals may provide a springboard for rapid variation of coronavirus
  131. Response of benthic invertebrate assemblages to seasonal and habitat condition in the Wewe River, Ashanti region (Ghana)
  132. Molecular record for the first authentication of Isaria cicadae from Vietnam
  133. Twig biomass allocation of Betula platyphylla in different habitats in Wudalianchi Volcano, northeast China
  134. Animal Sciences
  135. Supplementation of probiotics in water beneficial growth performance, carcass traits, immune function, and antioxidant capacity in broiler chickens
  136. Predators of the giant pine scale, Marchalina hellenica (Gennadius 1883; Hemiptera: Marchalinidae), out of its natural range in Turkey
  137. Honey in wound healing: An updated review
  138. NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block
  139. Radiotherapy for the treatment of pulmonary hydatidosis in sheep
  140. Retraction
  141. Retraction of “Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating microRNA-34a-5p/NOTCH1 signaling pathway”
  142. Special Issue on Reuse of Agro-Industrial By-Products
  143. An effect of positional isomerism of benzoic acid derivatives on antibacterial activity against Escherichia coli
  144. Special Issue on Computing and Artificial Techniques for Life Science Applications - Part II
  145. Relationship of Gensini score with retinal vessel diameter and arteriovenous ratio in senile CHD
  146. Effects of different enantiomers of amlodipine on lipid profiles and vasomotor factors in atherosclerotic rabbits
  147. Establishment of the New Zealand white rabbit animal model of fatty keratopathy associated with corneal neovascularization
  148. lncRNA MALAT1/miR-143 axis is a potential biomarker for in-stent restenosis and is involved in the multiplication of vascular smooth muscle cells
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