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Congenital adrenal hyperplasia. Role of dentist in early diagnosis

  • Michele Di Cosola , Francesca Spirito EMAIL logo , Khrystyna Zhurakivska , Riccardo Nocini , Roberto Lovero , Salvatore Sembronio , Luigi Santacroce , Edoardo Brauner , Giovanni Storto , Lorenzo Lo Muzio and Angela Pia Cazzolla
Published/Copyright: October 27, 2022

Abstract

Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by an impairment of steroid synthesis due to an altered production of 21-hydroxylase enzyme. Corticoid hormones are involved in the development and functioning of many organs. The aim of the present study was to review the international literature to collect data regarding oral manifestations of CAH. A review of the literature describing oral features of patients affected by CAH was performed using electronic databases (PubMed and Scopus). The data about number of patients, form of CAH, and oral findings were extracted and analyzed. Seven studies were included in the final analysis. The principal findings reported regarded an advanced dental development observed in patients with CAH. One paper reported amelogenesis imperfecta and periodontal issues. The dentist could be the first specialist involved in the CAH syndrome diagnosis, identifying the characteristic features described above, especially for the classical simple virilizing and non-classical form.

1 Introduction

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that, in the vast majority of cases, develops due to a mutation of sequence of the CYP21A2 gene. Such mutation leads to 21-hydroxylase (21-OH) deficiency that results in poor cortisol production and accumulation of precursor steroid hormones in the steroidogenic pathway [1,2]. Clinically, the manifestations range from mild to severe forms, distinguished as non-classical and classical CAH. The classical CAH occurs in about 1:15,000 live births and can assume two phenotypes: simple virilizing (SV) and salt wasting. The latter represents the most severe manifestation, in which a major shortage of 21-OH activity leads to an inadequate production of glucocorticoids and mineralocorticoids. The lack of aldosterone, if left untreated, can be incompatible with life, since it is fundamental for mineral salts homeostasis [3]. If the 21-OH activity is adequate to produce a sufficient amount of aldosterone, the CAH can manifest as SV (25% of all classical forms). In females, high levels of adrenal-derived androgens affect the development of the external genitalia, leading to their virilization, while males with SV form usually present an early virilization. A precocious pseudo puberty and hypocortisolism are also characteristics of both sexes [4].

Non-classical forms of CAH (NCAH) are characterized by around 20–50% of normal enzyme function and clinical manifestations are variable [5]. Patients may be asymptomatic at birth and primarily manifest symptoms at any age with signs of androgen excess. Frequently, the disease manifests with precocious pseudo puberty or polycystic ovary syndrome, hirsutism, and anovulation [5,6]. The therapies aim to address two issues: first, to replace deficient hormones, and second, to reduce excessive androgen levels.

In addition to the abovementioned manifestations, the organs and systems reported to be mainly influenced by such hormonal imbalance involve hypothalamus, cardiovascular system, bones, reproductive apparatus, musculoskeletal system, and skin [7].

Oral tissues are strongly influenced by steroid hormones. In particular, sex hormone receptors are widely present in the gingival tissue whose homeostasis is influenced by the blood fluctuation of these hormones [8]. Sex hormones group has been demonstrated to regulate cellular proliferation and differentiation in several tissues, among which keratinocytes and fibroblasts of the gingiva [9,10,11]. Estrogens increases the inflammatory component of gingiva, while progesterone plays a role in regulating the vascular permeability of the gingival and periodontal tissues, through the increase of prostaglandins production and polymorphonuclear leukocytes chemotaxis [12].

Several studies investigated the alteration of oral mucosa, gingiva, and periodontal tissue during the fundamental phases of hormonal development (i.e., puberty, menstrual cycle, pregnancy, and menopause in females), showing an important correlation between hormonal status and oral health [13].

In specific periods of woman’s hormonal development, when the estradiol and progesterone levels are the highest, an increase in inflammation and gingival bleeding has been noted, not correlated to the value of the plaque index which often culminates during gestation in the formation of a painless exophytic mass with a sessile or pedunculated base, defined as a “gravidic tumor” [9].

The aim of the present work is to review the existing literature to summarize the current knowledge about oral manifestations in patients with CAH in order to determine if any peculiar signs are associated and if the dentist could play a role in early diagnosis

2 Methods

This review was performed in order to answer the following question: “What are oral manifestations of CAH, if any?”

Electronic databases PubMed and Scopus were screened in order to search studies suitable for inclusion in this review. The following search strategy was used: [“congenital adrenal hyperplasia” AND (tooth OR teeth OR dental OR gingival OR oral manifestation OR oral mucosa)], [“adrenogenital” AND (tooth OR teeth OR dental OR oral manifestation OR oral mucosa)]. In addition, bibliographies of included studies were manually checked in order to identify other articles to be considered in this study. Only studies in English language and fulfilling the following criteria were eligible for inclusion:

  1. Studies reporting patients’ data with confirmed diagnosis of CAH.

  2. All study designs were considered (case reports, original papers, reviews, and conference proceedings).

  3. No restrictions about the year of publication were applied.

The articles, resulting from search strategy, were screened by title and abstract by two authors. If data reported in abstract were not sufficient for decision making, the full text reading was performed. So selected papers were full text examined and, if accordant with inclusion criteria, were included in the review. Any disagreement between authors was solved in a discussion.

The following data were extracted from the included studies:

  1. Authors’ names, year of publication, type of study design, number of patients, diagnosis, form of CAH, oral findings, and therapy.

3 Results

After application of search strategy, 181 records were identified. After removing duplicates, 63 records were screened by title and abstract evaluation and, subsequently, 10 were selected for full text examination. Two studies were excluded because they were written in non-English language [14,15], and for one study [16], only abstract was available. At the end, seven studies were included in the review [17,18,19,20,21,22,23]. Extracted data are summarized in Table 1.

Table 1

Data extracted from included studies

Authors Year Study design Number of patients Diagnosis Classical or non-classical form Oral findings Therapy
Bergstrand and Filipsson [17] 1967 Congress proceedings 22 (13 M and 9 F) Adrenogenital syndrome Classical Dental development is advanced in children with adrenogenital syndrome, but it is less influenced by androgens than skeletal development Cortisone
Wagner et al. [18] 1963 Original study 7 (2 M and 5 F) Congenital adrenocortical hyperplasia and adrenogenic virilism Classical Advanced dental development in children with congenital adrenocortical hyperplasia and androgen virilism Cortisone
Garn et al. [19] 1965 Original study 6 (2 M and 4 F) Virilizing adrenal hyperplasia Not indicated Advanced dental development Not indicated
Roberts et al. [20] 1985 Original study 9 (8 M and 1 F) Congenital adrenal hyperplasia Not indicated No significant abnormal dental development was detected Not indicated
Singer et al. [21] 2001 Case report 1 F Non-classic adrenal hyperplasia Early shedding of the primary teeth Hydrocortisone
Ajlan [22] 2015 Case report 1 F Congenital adrenal hyperplasia Classical Amelogenesis imperfecta (AI), localized aggressive periodontitis Prednisone and fludrocortisone
Angelopoulou et al. [23] 2015 Case report 1 M Congenital adrenal hyperplasia Classical Premature exfoliation of primary teeth, accelerated eruption of permanent dentition, tooth mobility, bone destruction Hydrocortisone and potassium levothyroxine

The data available in the literature resulted to be very scarce. The most recent studies [21,22,23] were case reports, presenting single cases of CAH patients and their oral features. The other included papers were original studies, but date back to the 60 s [18,19] and 80 s [20]. One of the papers was a congress proceeding extract [17]. However, even in the original studies, the sample of included patients was small.

Terms used in the studies to identify patients with CAH were: “Adrenogenital syndrome” [17], “Congenital adrenocortical hyperplasia” [18,20,21,22,23], “Adrenogenic virilism” [18], and “Virilizing adrenal hyperplasia” [19]. Regarding oral findings in patients with CAH, five studies reported an advanced dental development, [17,18,19,21,23] even if they noted that it was accelerated less than the acceleration of skeletal maturation observed in young patients. A study by Roberts et al. [20] concluded that no significant difference was observed between the affected patients and control group in terms of dental development. Meanwhile, one study [22] reported a case with other oral alterations: amelogenesis imperfecta and periodontitis in a patient with CAH.

4 Discussion

CAH is a genetic disorder resulting from an alteration of hormone production in the adrenal gland. It can result from the failure of any of the enzymes involved in the cascade of steroid hormone synthesis but in the vast majority of cases, it is caused by a deficiency of 21-OH [24]. The responsible gene is CYP21A2, for which over 100 mutations leading to various phenotypes have been reported [25,26,27]. Among these, the variant characterized by mutation 841G > T has been characterized and can be found in the CYP21A2 database created by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee (https://www.pharmvar.org/htdocs/archive/cyp21.htm) [28]. The clinical phenotype reported for such mutation is the NCAH, with an in vitro activity of 17-Hydroxyprogesterone/Progesterone of 50%/20%. The residual 21-OH enzyme activity, in such patients, leads to androgen excess, but also to some cortisol and aldosterone deficiency [6,29,30]. NCAH forms are not usually characterized by virilization of genitalia and diagnosis is typically made in adolescence or adulthood [5,31]. In most of the reported cases, the first diagnosis was made after the onset of premature pubarche and hirsutism [31], confirmed by specific hormonal dosage and genetic analysis [5]. The prevalence of NCAH varies widely for different ethnicities, being reported to affect about 0.1% of Caucasian population and reach 3.7% in Ashkenazi Jews [32].

Regarding the treatment of NCAH, it has been suggested that a stimulated cortisol level of less than 500 nmol/L may justify daily glucocorticoid supplementation [33].

Steroid hormones represent a fine regulator of various functions of our organism [34]. And their imbalance, as well as a substitution therapy, can lead to various undesirable consequences, more or less serious. In non-classical forms, fortunately, the damage of the various organs and functions is limited, compared to the classical form [35,36,37].

Oral cavity, with its hard and soft tissues, is often the site of manifestation of several systemic and genetic diseases [38,39,40,41,42]. The role of sex steroid hormones on periodontal tissues has been widely documented [9,11,13,43]. Androgen receptors have been identified in human oral mucosa by Ojanotko-Harri et al. [44] in 1992, indicating their location in epithelial cells, fibroblasts, and endothelial cells. Estrogen is the main sex steroid hormone responsible for alterations in blood vessels of target tissues in females [45]. The variation in its levels also affects the vascularization of the periodontal tissues, exposing women to para-physiological conditions of the periodontium in periods such as puberty, ovulation, pregnancy, and many other causes [13]. Progesterone has been demonstrated to lead to the accumulation of inflammatory cells in blood vessels, increase vascular permeability and increase vascular proliferation. The presence of steroid receptors on immune system components has been identified in several studies [9,46].

All these data suggest that a disease such as CAH can also lead to oral manifestations.

The present review aimed to identify all existing information about oral manifestations in patients with CAH. However, the data in the literature were very scarce and there is lack of original studies with an adequate sample to be able to draw any conclusion. It appears that in children with CAH, there is a tendency for their dentition to develop early. Although in most of the studies included in this review, there is no clear identification of the classical and non-classical forms, it can be assumed that the more severe oral manifestations are characteristic of the classical forms [17,18,22,23].

Considering the demonstrated influence of steroid hormones on inflammation state of the periodontal tissues and therefore the possible increased risk of developing periodontitis in patients with CAH, further studies are certainly needed to investigate the role of early inflammatory biomarkers in CAH patients.

The dentist could be the first specialist involved in the CAH syndrome diagnosis, identifying the characteristic features described above, especially for the classical SV and non-classical form.

Acknowledgments

Not applicable.

  1. Funding information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  2. Author contributions: Conceptualization: M.D.C. and E.B.; methodology: M.D.C. and K.Z.; validation: L.L.M.; investigation: F.S., G.S., and L.S.; data collection: L.S. and A.P.C.; writing – original draft preparation: C.P., K.Z., and R.L.; writing – review and editing: F.S. and L.L.M.; visualization: S.S.; supervision: R.N. and L.L.M. All authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: The authors declare no conflict of interest. Lorenzo Lo Muzio serves as Editor in Open Medicine, but it did not affected peer-review process.

  4. Data availability statement: All data generated or analyzed during this study are included in this published article.

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Received: 2022-01-19
Revised: 2022-05-24
Accepted: 2022-06-21
Published Online: 2022-10-27

© 2022 Michele Di Cosola et al., published by De Gruyter

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

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  59. The relationship between night shift work and breast cancer incidence: A systematic review and meta-analysis of observational studies
  60. LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis
  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
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