Volume 31, Issue 6

A novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes COVID-19 infections penetrates body cells by binding to angiotensin-converting enzyme-2 (ACE2) receptors. Evidence shows that SARS-CoV-2 can also affect the urogenital tract. Hence, it should be given serious attention when treating COVID-19-infected male patients of reproductive age group. Other viruses like HIV, mumps, papilloma and Epstein–Barr can induce viral orchitis, germ cell apoptosis, inflammation and germ cell destruction with attending infertility and tumors. The blood-testis barrier (BTB) and blood-epididymis barrier (BEB) are essential physical barricades in the male reproductive tract located between the blood vessel and seminiferous tubules in the testes. Despite the significant role of these barriers in male reproductive function, studies have shown that a wide range of viruses can still penetrate the barriers and induce testicular dysfunctions. Therefore, this mini-review highlights the role of ACE2 receptors in promoting SARS-CoV-2-induced blood-testis/epididymal barrier infiltration and testicular dysfunction.

High-mobility group box 1 (HMGB1), also called amphoterin, HMG1 and p30, is a highly conserved protein between different species that has various functions in nucleus such as stabilization of nucleosome formation, facilitation of deoxyribonucleic acid (DNA) bending and increasing the DNA transcription, replication and repair. It has also been indicated that HMGB1 acts as a potent pro-inflammatory cytokine with increasing concentrations in acute and chronic inflammatory diseases. Asthma is a common chronic respiratory disease associated with high morbidity and mortality rates. One central characteristic in its pathogenesis is airway inflammation. Considering the inflammatory role of HMGB1 and importance of inflammation in asthma pathogenesis, a better understanding of this protein is vital. This review describes the structure, cell surface receptors, signaling pathways and intracellular and extracellular functions of HMGB1, but also focuses on its inflammatory role in asthma. Moreover, this manuscript reviews experimental and clinical studies that investigated the pathologic role of HMGB1.

Objectives Multiple sclerosis (MS) is a progressive and often debilitating neurological disorder. This chronic disease has a high prevalence in the world and also in Iran. Fatigue is a common symptom of the disease, which causes serious mental and psychological discomfort. Simple saffron syrup, contains some compounds that can be effective in relieving the symptom. The object of this study is to investigate the effect of simple saffron syrup on fatigue in patients with MS. Methods This study is a pre-post study which evaluates the fatigue rate of MS patients (30 participants) according to the FSS scale. The participants were given a saffron simple syrup to consume a tablespoon (7.5 cc) every 8 h for two months. After 60 days of prescribing, patients are assessed for fatigue based on fatigue severity scale (FSS) criteria. Results One-way ANOVA showed that there was a notable difference between the mean score of fatigue in MS patients before and after the intervention (p<0.001). So, the fatigue severity of the subjects after saffron syrup consumption dropped dramatically for two months. (p<00.01). Conclusions According to the outcomes of this study, simple saffron syrup can be effective as an adjunct therapy for fatigue reduction in patients with MS due to effectiveness besides no significant side effects.

Background In previous studies, we have observed that glutamate antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the elevated plus maze (EPM) test in rats. In the present study, the effect of Atenolol, a specific Beta Adreno-receptor antagonist in the EPM was studied in male rats bilaterally cannulated NAS. Methods Rats were divided into five groups that received either 1 μL injections of saline or atenolol in different doses (0.75, 1 or 2 μg/1 μL, n=15–16) 15 min before testing. Results Time Spent in the Open Arm was modified by treatment (F=4.563, p=0.006, df 3). This was increased by the lowest dose of atenolol (p<0.05), by the medium doses (p<0.001) and also by the highest dose (p<0.01). Time per Entry was modified by treatment (F=4.54, p=0.06, df 3). This parameter was increased by the lowest dose of atenolol (p<0.01), but not for the medium and higher doses. Conclusions We conclude that Atenolol beta receptor blockade in the accumbens lead to an anxiolytic-like effect related to an increase in the time spent in the open arm and in the time per entry, showing specific behavioral patterns.

Objectives The present study was designed to investigate the effectiveness of trihexyphenidyl, a central anticholinergic drug, in preventing the post-traumatic stress disorder (PTSD) symptoms in a mouse model. Methods Mice were subjected to underwater trauma stress for 30 s on day 1 followed by three situational reminders (3rd, 7th and 14th day). Thereafter, the behavioral alterations including freezing behavior were noted on 21st day. The serum corticosterone levels were measured as a biochemical marker of trauma. Elevated plus maze test was done on day 1 and day 2 to assess the memory formation following exposure to trauma. Results Trauma and situational reminders were associated with a significant development of behavioral changes and freezing behavior on the 21st day. Moreover, there was also a significant decrease in the serum corticosterone levels. A single administration of trihexyphenidyl (2 and 5 mg/kg) significantly restored trauma associated-behavioral changes and serum corticosterone levels. Moreover, it significantly increased the transfer latency time on day 2 following stress exposure in comparison to normal mice suggesting the inhibition of memory formation during trauma exposure. Trihexyphenidyl also led to significant reduction in freezing behavior in response to situational reminders again suggesting the inhibition of formation of aversive fear memory. Conclusion The blockade of central muscarinic receptors may block the formation of aversive memory during the traumatic event, which may be manifested in form of decreased contextual fear response during situational reminders. Central anticholinergic agents may be potentially useful as prophylactic agents in preventing the development of PTSD symptoms.

Background Interleukin-23 (IL-23), a key inflammatory regulator in the pathogenesis of psoriasis, is suspected to play a role in the onset of pulmonary dysfunction (chronic obstructive pulmonary disease) in psoriasis. Despite that, pulmonary function tests are rarely studied in these subjects. This study aims to seek a possible relation between pulmonary function in psoriasis patients serum IL-23. Methods For this analytical cross-sectional study, male psoriasis patients in the age group of 25–45 years were recruited from dermatology out patient department (n = 40). Age and BMI matched apparently healthy individuals were recruited as control group (n = 40). After obtaining demographic and personal details, anthropometric parameters and blood pressure were recorded. The severity of psoriasis was assessed using Psoriasis Area and Severity Index score. Pulmonary function was assessed using computerized spirometry, and serum IL-23 was measured using ELISA. Results Forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow rate, and forced expiratory flow at 25%–75% of the pulmonary volume (FEF25%–75%) were significantly reduced in psoriasis. Based on the percentage of predicted values FEF25%–75% was significantly reduced in psoriasis. Serum IL-23 (pg/mL) was significantly higher in psoriasis. The increase in IL-23 in psoriasis subjects does not correlate with their pulmonary function. Conclusions Psoriasis may be associated with a reduced lung function even when the disease is in the mild stage. Increased IL-23 found in these subjects is suggestive of systemic inflammation, which indirectly lowers lung function.

Objectives Steroid-induced ocular hypertension and glaucoma are associated with extracellular matrix remodeling at the trabecular meshwork (TM) of the eye due to reduced secretion of matrix metalloproteinases (MMPs), a family of enzymes regulating extracellular matrix proteolysis. Several biological functions of steroids are known to involve regulation of adenosine A1 receptors (A1AR) and nuclear factor kappa B (NFKB). Since MMPs expression in TM has been shown to be regulated by A1AR as well as transcription factors, it is likely that dexamethasone-induced changes in aqueous humor dynamics involve reduced MMP and A1AR expression and reduced NFKB activation. Hence, the current study investigated the association of dexamethasone-induced reduction in MMP secretion with reduced NFKB activation and A1AR expression. Methods Human trabecular meshwork cells (HTMCs) were characterized by estimating myocilin and alpha smooth muscle actin expression and then were treated with dexamethasone 100 nM for 2, 5 and 7 days. The MMP secretion was estimated in culture media using Western blot. Immunocytochemistry (ICC) and ELISA were done to investigate the effect of dexamethasone on NFKB phosphorylation. A1AR expression in HTMCs was determined using Western blot and ELISA. Results Dexamethasone caused a significant reduction in both MMP-2 and -9 expression compared to untreated group after five and seven days but not after two days of culture. Significantly reduced phosphorylated NFKB and A1AR protein levels were detected in dexamethasone treated compared to vehicle treated HTMCs after five days of culture. Conclusions Dexamethasone reduces MMP-2 and -9 secretion by HTMCs and this effect of dexamethasone is associated with reduced NFKB phosphorylation and A1AR expression.

Background Bidens pilosa (BP) possessed anti-inflammatory, antioxidant, and immunomodulatory activities. Its beneficial effects on intestinal inflammation and oxidative stress in 2,4,6 trinitrobenzene sulfonic acid (TNBS) induced colitis in Wistar rats was evaluated. Methods Thirty female Wistar rats weighing 180–200 g were distributed into six groups (n = 5): non-colitic, untreated colitic and colitic rats treated graded doses of methanol extract of BP (50–400 mg/kg). Colitis was induced in rats by intracolonic instillation of 0.2 mL of 40 mg/mL TNBS. BP was administered two days pre-colitis induction and treatments continued until seven days post-colitis induction. A day after the last treatment, rats were euthanized, colon removed aseptically and response to treatment assessed. Phytochemical composition of BP was determined using the GC-MS. Results BP significantly reduced macroscopic colonic damage score, weight/length ratio, colonic lipid peroxidation level, leukocytes infiltration, and TNF- α level in comparison to untreated colitic rats (p ≤ 0.008). Similarly, treatment with 200 and 400 mg/kg BP prevented depletion of colonic glutathione level than other treatment groups (p ≤ 0.0002). Histological findings revealed that treatment with 400 mg/kg BP significantly preserved the mucosal epithelial layer. It also prevented ulceration and sloughing of the mucosal layers and reduced infiltration of inflammatory cells compared to other treatment groups. Among the 16 compounds identified were oleic acid (6.2%) and n- hexadecanoic acid (2.0%) with antioxidant anti-inflammatory activities. Conclusions The beneficial effects of BP in rat colitis might be related to the reduction of leucocytes infiltration, inhibition of oxidative stress and pro-inflammatory cytokines.

Objectives AAA (Allgrove) syndrome is a rare genetic disorder characterized by cardinal features of adrenal insufficiency, achalasia, and alacrimia. Case presentation A 21 year girl of known case of Triple A syndrome was referred for the evaluation of autonomic function. She was born full term with developmental delay and abnormal gait. Esophageal manometry study by pneumatic balloon dilatation revealed the presence of achalasia cardia. She had signs of peripheral neuropathy and had episodes of fainting and suspected orthostatic hypotension. Cardiovascular autonomic function and heart rate variability tests were conducted as per Ewing protocol, revealed that the patient had sympathovagal imbalance and sympathetic dominance. Conclusions The presence of autonomic dysfunction adds the 4th A to the Triple A syndrome (Adrenal insufficiency, Achalasia, Alacrimia and Autonomic dysfunction). Noninvasive autonomic function tests are recommended for Triple A syndrome patients to reduce the morbidity associated with autonomic dysfunction.

Objectives The number of coronavirus disease (COVID-19) cases is increasing in Bangladesh. Many people have suffered from symptoms like COVID-19 during this pandemic, and some people have cured without taking any treatment or taking minor pharmacological and non-pharmacological treatments. However, they might be spreading their infections among their family members and perhaps in the community. It is unsure that individuals with COVID-19-like symptoms are positive with COVID-19, but our concern is, during this pandemic, any types of symptoms such as flu-like symptoms should have been taken seriously. This study was observed in the cases from three families with COVID-19 like symptoms. Case presentation This observational study was done between May 20 and Jun 2, 2020, in Bangladesh. The members of the inspected families shared COVID-19 like symptoms that were lasted for 3-10 days. Conclusions COVID-19 might be spread and cured silently in Bangladesh, which recommends that awareness is needed throughout the country to prevent the spreading of the disease.