Evaluation of novel 2-(quinoline-2-ylthio)acetamide derivatives linked to diphenyl-imidazole as α-glucosidase inhibitors: Insights from in silico, in vitro, and in vivo studies on their anti-diabetic properties.

The inhibition of the α-glucosidase enzyme is crucial for targeting type 2 diabetes mellitus (DM). This study introduces a series of synthetic analogs based on thiomethylacetamide-quinoline derivatives linked to diphenyl-imidazole as highly potential α-glucosidase inhibitors. Twenty derivatives were synthesized and screened in vitro against α-glucosidase, revealing IC50 values ranging from 0.18 ± 0.00 to 2.10 ± 0.07 µM, in comparison to the positive control, acarbose. Among these derivatives, compound 10c (IC50 = 0.180 µM) demonstrated the highest potency and revealed a competitive inhibitory mechanism in kinetic studies (Ki = 0.15 µM). Docking and molecular dynamic evaluations elucidated the binding mode of 10c with the active site residues of the α-glucosidase enzyme. Moreover, in vivo assessments on a rat model of DM affirmed the anti-diabetic efficacy of 10c, evidenced by reduced fasting and overall blood glucose levels. The histopathological evaluation enhanced pancreatic islet architecture and hepatocytes in liver sections. In conclusion, novel 2-(quinoline-2-ylthio)acetamide derivatives as potent α-glucosidase inhibitors were developed. Compound 10c emerged as a promising candidate for diabetes management, warranting further investigation for potential clinical applications and mechanistic insights.

Prevalence of thyroid dysfunction among Iranian older adults: a cross-sectional study.

There is limited data on the prevalence of thyroid dysfunction in the older population. This study aimed to determine the prevalence of thyroid dysfunction among a sample of Iranian older adults. A cross-sectional analysis of older adults who aged 60 years and over was conducted. A total of 363 subjects were randomly selected from Birjand longitudinal aging study (BLAS) cohort study. Serum thyroid-stimulating hormone (TSH) level, total thyroxine (T4) and total triiodothyronine (T3) were measured by the enzyme-linked immunosorbent assay (ELISA). Based on thyroid function tests and history of taking medicines used to treat thyroid disorders, participants were classified into the following groups: euthyroid, overt/subclinical hypothyroidism, and overt/subclinical hyperthyroidism. Subsequently, the crude and World Health Organization (WHO) age-standardized prevalence were estimated for different thyroid function categories. A total of 171 men and 192 women, aged 60-94 years, were randomly selected. The crude prevalence of total hypothyroidism was 22.31% (subclinical [18.46%], overt [3.86%]), and that of hyperthyroidism was 1.66% (subclinical [1.38%], overt [0.28%]). The crude prevalence of total thyroid dysfunction was, therefore, 23.97%. A female preponderance was noticed in both total (P-value = 0.035) and overt (P-value = 0.035) hypothyroidism. An increasing trend with age was noticed in the prevalence of total hypothyroidism (P-value = 0.049). Age-standardized prevalence of total hypothyroidism and hyperthyroidism was 26.63% (95% confidence interval [CI] 20.58-33.69%) and 1.11% (95% CI 0.49-2.51%), respectively. A considerable proportion of our study population demonstrated evidence of thyroid dysfunction, particularly subclinical hypothyroidism. Our findings highlight the importance of further investigation of thyroid disorders among older Iranian adults.

Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population.

Polycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O-H-P, H-P, O-H, and O-P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18-40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O-H-P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02-6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O-H-P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.

Serum Vitamin D Status and Cognitive Function in Iranian Older Adults: Evidence from the Birjand Longitudinal Aging Study.

BACKGROUND: There is evidence of the role of vitamin D deficiency in cognitive decline. However, the results of studies regarding the relationship between the reduction of vitamin D concentrations and cognitive impairment are heterogeneous. OBJECTIVES: We aimed to answer the question of whether vitamin D deficiency is associated with cognitive decline in older adults. METHODS: In this cross-sectional study, the baseline data of the Birjand Longitudinal Aging Study (BLAS) were analyzed. Of 1420 participants in the BLAS, 1219 participants aged ≥60 y old were included in the present study. Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by the enzyme-linked immunosorbent assay method. The 6-item Cognitive Impairment Test (6-CIT), Mini-Mental State Examination (MMSE), Category Fluency Test (CFT), and Abbreviated Mental Test Score (AMTS) were used to assess cognitive function. Multiple logistic regression analysis, adjusted for potential confounders, was employed to estimate the association between cognitive function and 25(OH)D concentrations. RESULTS: Among study participants, 905 (74.24%) had sufficient vitamin D concentrations (≥20 ng/ml), 209 (17.15%) had insufficient vitamin D concentrations (12-20 ng/ml), and 105 (8.61%) had vitamin D deficiency (<12 ng/ml). There was no significant correlation between serum 25(OH)D concentrations and scores of 6-CIT (P = 0.279), AMTS (P = 0.181), MMSE (P = 0.118), and CFT (P = 0.259). Also, the prevalence of cognitive impairment had no significant relationship with vitamin D status. Finally, in the multiple logistic regression analysis, there was no association between the insufficient or deficient concentrations of 25(OH)D and impaired cognitive function both before and after adjustment for various cofounders. CONCLUSIONS: The present study found no significant association between vitamin D status and cognitive impairment.

Effects of Smoking on COVID-19 Management and Mortality: An Umbrella Review.

Introduction: Smoking status appears to lead to a poor prognosis in COVID-19 patients. However, findings from the studies conducted on this topic have not been consistent, and further exploration is required. Methods: The objective of this umbrella review was to examine the effects of smoking on COVID-19 management and mortality. Online databases that included PubMed, Embase, Scopus, and Web of Science were searched using relevant keywords up to July 27, 2022. Articles were restricted to the English language, and the PRISMA protocol was followed. Results: A total of 27 systematic reviews, published from 2020 to 2022, were included. Individual studies included in the systematic reviews ranged from 8 to 186, with various population sizes. The consensus from the majority of systematic reviews was that COVID-19 smoker patients experience greater disease severity, disease progression, hospitalization rate, hospital admission duration, mechanical ventilation, ICU admission, and mortality rate. Conclusions: COVID-19 patients with a history of smoking (current and former) are vulnerable to adverse hospital outcomes and worse COVID-19 progression. Effective preventive and supportive approaches are required to decrease the risk of COVID-19 morbidity and mortality in patients with a history of smoking.

Diagnostic accuracy of circular RNA for diabetes Mellitus: a systematic review and diagnostic Meta-analysis.

BACKGROUND: This study aimed to investigate the pooled diagnostic ability of circular RNA (circRNA) molecules for diabetes mellitus. METHODS: We searched PubMed, Scopus, and Web of Science for relevant studies. A total of 2070 participants, including 775 diabetic patients and 1295 healthy individuals, from five studies were included in this meta-analysis. True positive, true negative, false positive, and false negative data were extracted to calculate pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristics curve. The Deeks' funnel plot was applied for publication bias assessment, Cochran's Q test and I2 index were applied for inter-study heterogeneity assessment. Besides, a subgroup analysis was performed for determining the source of heterogeneity between studies. P value < 0.05 was considered significance. All analysis were done by STATA version 14. RESULTS: CircRNA presented a sensitivity of 76% (95% confidence interval [95%CI]: 66-84%), specificity of 77% (95%CI: 58-89%), positive LR of 3.25 (95%CI: 1.69-6.23), negative LR of 0.31 (95%CI: 0.21-0.46), DOR of 10.41 (95%CI: 4.26-25.41), and AUC of 0.82 (95%CI: 0.79-0.85) for diabetes mellitus detection. More specifically, hsa_circ_0054633 showed a sensitivity of 67% (95%CI: 53-81%) and a specificity of 82% (95%CI: 63-100%). CONCLUSION: CircRNAs show highly accurate diagnostic capability for type 2 diabetes mellitus and gestational diabetes mellitus. High sensitivity of circRNAs introduces them as potential noninvasive biomarkers for early diagnosis of diabetes mellitus and their high specificity introduces them as potential therapeutic targets by regulation of their expression.

The Association of Oral Microbiome Dysbiosis with Gastrointestinal Cancers and Its Diagnostic Efficacy.

BACKGROUND: The second leading mortality cause in the world is cancer, making it a critical issue that impacts human health. As a result, scientists are looking for novel biomarkers for cancer detection. The oral microbiome, made up of approximately 700 species-level taxa, is a significant source for discovering novel biomarkers. In this review, we aimed to prepare a summary of research that has investigated the association between the oral microbiome and gastrointestinal cancers. METHODS: We searched online scientific datasets including Web of Science, PubMed, Scopus, and Google Scholar. Eligibility criteria included human studies that reported abundances of the oral microbiome, or its diagnostic/prognostic performance in patients with gastrointestinal cancers. RESULTS: Some phyla of the oral microbiome have a relationship with cancers. Some particular phyla of the oral microbiome that may be related to gastrointestinal cancers consist of Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria. Changes in the abundances of Porphyromonas, Fusobacterium, Prevotella, and Veillonella are correlated with carcinogenesis, and may be used for distinguishing cancer patients from healthy subjects. Oral, colorectal, pancreatic, and esophageal cancers are the most important cancers related to the oral microbiome. CONCLUSION: The results of this study may help future research to select bacteria as an early diagnostic or prognostic biomarker of gastrointestinal cancer. Given the current state of our knowledge, additional research is required to comprehend the multiplex processes underlying the role of bacterial microbiota upon cancer progression and to characterize the complex microbiota-host interaction network.

Estimating Methods of the Undetected Infections in the COVID-19 Outbreak: A Systematic Review.

INTRODUCTION: The accurate number of COVID-19 cases is essential knowledge to control an epidemic. Currently, one of the most important obstacles in estimating the exact number of COVID-19 patients is the absence of typical clinical symptoms in a large number of people, called asymptomatic infections. In this systematic review, we included and evaluated the studies mainly focusing on the prediction of undetected COVID-19 incidence and mortality rates as well as the reproduction numbers, utilizing various mathematical models. METHODS: This systematic review aims to investigate the estimating methods of undetected infections in the COVID-19 outbreak. Databases of PubMed, Web of Science, Scopus, Cochrane, and Embase, were searched for a combination of keywords. Applying the inclusion/exclusion criteria, all retrieved English literature by April 7, 2022, were reviewed for data extraction through a two-step screening process; first, titles/abstracts, and then full-text. This study is consistent with the PRISMA checklist. RESULTS: In this study, 61 documents were retrieved using a systematic search strategy. After an initial review of retrieved articles, 6 articles were excluded and the remaining 55 articles met the inclusion criteria and were included in the final review. Most of the studies used mathematical models to estimate the number of underreported asymptomatic infected cases, assessing incidence and prevalence rates more precisely. The spread of COVID-19 has been investigated using various mathematical models. The output statistics were compared with official statistics obtained from different countries. Although the number of reported patients was lower than the estimated numbers, it appeared that the mathematical calculations could be a useful measure to predict pandemics and proper planning. CONCLUSION: In conclusion, our study demonstrates the effectiveness of mathematical models in unraveling the true burden of the COVID-19 pandemic in terms of more precise, and accurate infection and mortality rates, and reproduction numbers, thus, statistical mathematical modeling could be an effective tool for measuring the detrimental global burden of pandemic infections. Additionally, they could be a really useful method for future pandemics and would assist the healthcare and public health systems with more accurate and valid information.

Antioxidative hypoglycemic herbal medicines with in vivo and in vitro activity against C-reactive protein; a systematic review.

BACKGROUND: Inflammation is a double-edged sword in the pathophysiology of chronic diseases, such as type 2 diabetes mellitus (T2DM). The global rise in the prevalence of T2DM in one hand, and poor disease control with currently-available treatments on the other hand, along with an increased tendency towards the use of natural products make scientists seek herbal medicines for the management of diabetes and its complications by reducing C-reactive protein (CRP) as an inflammatory marker. PURPOSE: To systematically review the literature to identify the efficacy of various medicinal plants with antioxidative and anti-inflammatory properties considering their effect on CRP in animal models of T2DM. STUDY DESIGN: systematic review. METHODS: Electronic databases including PubMed, Scopus, Web of Science and Cochran Library were searched using the search terms "herbal medicine", "diabetes", "c-reactive protein", "antioxidants" till August 2021. The quality of evidence was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE's) tool. The study protocol was registered in PROSPERO with an ID number CRD42020207190. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Among total of 9904 primarily-retrieved articles, twenty-three experimental studies were finally included. Our data indicated that numerous herbal medicines, compared to placebo or hypoglycemic medications, are effective in treatment of diabetes and its complications through decreasing CRP concentrations and oxidative stresses levels. Medicinal plants including Psidium guajava L., Punica granatum L., Ginkgo biloba L., Punica granatum L., Dianthus superbusn L.. Moreover, Eichhornia crassipes (Mart.) Solms, Curcuma longa L., Azadirachta indica A. Juss., Morus alba L., and Ficus racemosa L. demonstrated potential neuroprotective effects in animal models of diabetes. CONCLUSION: Hypoglycemic medicinal plants discussed in this review seem to be promising regulators of CRP, and oxidative stress. Thus, these plants are suitable candidates for management of diabetes' complications. Nevertheless, further high-quality in vivo studies and clinical trials are required to confirm these effects.

Previously Unreported Esophageal Lymphoid Polyp in a Child: A Case Report with Histopathology.

Introduction: Benign esophageal tumors are uncommon; most are detected by chance upon endoscopy. Lymphoid polyps, like those of the small and large intestine, have not been reported to occur in the esophagus. We describe an esophageal benign lymphoid polyp. Case Report: A 7.5-year-old girl was referred with dysphagia. Upper endoscopy demonstrated and removed a single small pedunculated polyp in the upper third of the esophagus. The polyp consisted of two hyperplastic lymphoid aggregates in the lamina propria covered by stratified non-keratinizing squamous epithelium. Discussion: Esophageal polyps may be produced by hyperplastic lymphoid tissue and may be a cause of dysphagia.

The association between advanced glycation end products (AGEs) and ABC (hemoglobin A1C, blood pressure, and low-density lipoprotein cholesterol) control parameters among patients with type 2 diabetes mellitus.

BACKGROUND: Diabetes-induced chronic hyperglycemia results in the formation and aggregation of advanced glycation end-products (AGEs), which are products of non-enzymatic glycosylation of lipids or proteins. The development of diabetic complications can be accelerated by AGEs. In the current study, we aimed to explore the relationship between AGEs levels and ABC goals of diabetes control (A: Hemoglobin A1C < 7.0%, B: Blood pressure < 140/90 mmHg, and C: low-density lipoprotein cholesterol [LDL] < 100 mg/dL). METHODS: In the current cross-sectional study, 293 patients with type 2 diabetes mellitus (T2D), were enrolled. Demographic and clinical characteristics of the individuals were collected. AGEs levels were measured using quantitative fluorescence spectroscopy. Finally, the association of AGEs levels with patients' characteristics and ABC goals was assessed. RESULTS: Higher serum AGEs concentration was detected in older age, smoking patients and those with higher diastolic blood pressure, lower high-density lipoprotein (HDL) level, lower body mass index (BMI) and retinopathy. Moreover, the T2D patients who achieved higher numbers of ABC goals of diabetes were younger age (P-value = 0.003), with lower hemoglobin A1C (P-value = 0.001), fasting blood sugar (P-value = 0.002) diastolic blood pressure (P-value = 0.001), systolic blood pressure (P-value = 0.001), cholesterol (P-value = 0.001), LDL (P-value = 0.001), and AGEs (P-value = 0.023) levels. Diabetic patients with AGEs levels above 73.9% were about 2.2 times more likely to achieve none of ABC treatment goals (95% CI 1.107-3.616). CONCLUSION: Our results revealed the relationship between AGEs and ABC goal achievement, and microvascular diabetic complications, and imply that AGEs measurement may be valuable in the monitoring of diabetic patients' complications and treatment adjustment.

Circular RNAs in Alzheimer's Disease: A New Perspective of Diagnostic and Therapeutic Targets.

BACKGROUND: Circular RNAs (circRNAs), as covalently closed single-stranded noncoding RNA molecules, have been recently identified to involve in several biological processes, principally through targeting microRNAs. Among various neurodegenerative diseases (NDs), accumulating evidence has proposed key roles for circRNAs in the pathogenesis of Alzheimer's disease (AD); although the exact relationship between these RNA molecules and AD progression is not clear, they have been believed to mostly act as miRNA sponges or gene transcription modulators through correlating with multiple proteins, involved in the accumulation of Amyloid ß (Aß) peptides, as well as tau protein, as AD's pathological hallmark. More interestingly, circRNAs have also been reported to play diagnostic and therapeutic roles during AD progression. OBJECTIVE: Literature review indicated that circRNAs could essentially contribute to the onset and development of AD. Thus, in the current review, the circRNAs' biogenesis and functions are addressed at first, and then the interplay between particular circRNAs and AD is comprehensively discussed. Eventually, the diagnostic and therapeutic significance of these noncoding RNAs is highlighted in brief. RESULTS: A large number of circRNAs are expressed in the brain. Thereby, these RNA molecules are noticed as potential regulators of neural functions in healthy circumstances, as well as neurological disorders. Moreover, circRNAs have also been reported to have potential diagnostic and therapeutic capacities in relation to AD, the most prevalent ND. CONCLUSION: CircRNAs have been shown to act as sponges for miRNAs, thereby regulating the function of related miRNAs, including oxidative stress, reduction of neuroinflammation, and the formation and metabolism of Aß, all of which developed in AD. CircRNAs have also been proposed as biomarkers that have potential diagnostic capacities in AD. Despite these characteristics, the use of circRNAs as therapeutic targets and promising diagnostic biomarkers will require further investigation and characterization of the function of these RNA molecules in AD.

Demographic aspects, clinical characteristics, and therapeutic approaches in geriatric psoriasis: A study from a tertiary center.

Geriatric psoriasis, due to its unusual clinical manifestations and higher rates of systemic complications in this age group, is a challenging issue for dermatologists. Therefore, we aimed to provide an overview of the epidemiological, clinical, and therapeutic consequences among patients aged over 60 years with psoriasis in a referral center in Iran. This cross-sectional study was conducted on 156 patients over 60 years with the definitive diagnosis of psoriasis that were referred to our center between 2015 and 2019. By reviewing the recorded files of the patients, baseline characteristics including demographics, underlying comorbidities, age of disease onset, clinical type of the disease, clinical manifestations, and therapeutic approaches were extracted. The most common clinical feature was plaque type (73.1%) followed by pustular type (10.9%). The most frequent involved zone was the lower extremities (84.6%). Most of the patients were treated topically (87.1%), while as the most frequent systemic approaches, methotrexate and acitretin were considered for 74.4% and 60.3%, respectively. A significantly higher mean age at disease onset was found in female patients compared to male patients. The plaque type was more prevalent in men than in women. Also, the chance of nail involvement was 2.43 times higher in men than in women (p = 0.011, 95%CI: 1.22-4.84). The disease duration was significantly longer in patients suffering from plaque compared to those without this feature. Conversely, those with palmoplantar type experienced shorter disease duration. Psoriatic arthritis was also revealed in patients of lower ages. As in other societies, in our society, clinical characteristics, disease involvement patterns, as well as considered treatment approaches, can be influenced by demographic characteristics.

In vitro cell-based models of drug-induced hepatotoxicity screening: progress and limitation.

Drug-induced liver injury (DILI) is one of the major causes of post-approval withdrawal of therapeutics. As a result, there is an increasing need for accurate predictive in vitro assays that reliably detect hepatotoxic drug candidates while reducing drug discovery time, costs, and the number of animal experiments. In vitro hepatocyte-based research has led to an improved comprehension of the underlying mechanisms of chemical toxicity and can assist the prioritization of therapeutic choices with low hepatotoxicity risk. Therefore, several in vitro systems have been generated over the last few decades. This review aims to comprehensively present the development and validation of two-dimensional (2D) and three-dimensional (3D) culture approaches on hepatotoxicity screening of compounds and highlight the main factors affecting predictive power of experiments. To this end, we first summarize some of the recognized hepatotoxicity mechanisms and related assays used to appraise DILI mechanisms and then discuss the challenges and limitations of in vitro models.

Previously Unreported Pseudomembranous Duodenitis: A Case Report With Histopathology.

The pseudomembranous inflammatory process is a process characterized by the formation of a white membrane-like exudate over colonic mucosa and is mainly caused by Clostridium difficile toxin. The stool culture is considered to be the gold standard and is technically challenging and is not performed routinely. There are some reports of duodenitis and proximal jejunitis in horses attributed to Clostridium difficile infection. Hereby, we report a case of pseudomembranous duodenitis in a seven-year-old boy with a complaint of severe abdominal pain. Upper endoscopy revealed patchy ulceration and a white membrane in the duodenum. A biopsy was taken with the impression of a fungal infection. The histological study revealed crater-like ulceration with upward exudation of mucus consistent with the pseudomembranous inflammatory process. To the best of our knowledge, pseudomembranous duodenitis is not reported in the human as yet.

Characteristics of published/registered clinical trials on COVID-19 treatment: A systematic review.

OBJECTIVES: Due to the rapid spread of COVID-19 worldwide, many countries have designed clinical trials to find efficient treatments. We aimed to critically report the characteristics of all the registered and published randomized clinical trials (RCTs) conducted on COVID-19, and summarize the evaluation of potential therapies developed in various regions. EVIDENCE ACQUISITION: We comprehensively searched PubMed, Cochrane Library, Web of Science, Scopus, and Clinicaltrial.gov databases to retrieve all the relevant studies up to July 19, 2021, in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. We included all English-language published/registered RCTs on COVID-19, and excluded non-RCT, in-vitro/in-vivo, editorials, and review studies. Two reviewers independently evaluated all the records, and then analyzed by using SPSS 17. RESULTS: Within 3018 included studies, 2801 (92.8%) and 217 (7.2%) were registered or published RCTs consisting of about 600 synthetic drugs. Herbal medicines have been studied in 23 trials (10.6%) among the published RCTs and in 357 registered RCTs (12.7%). Hydroxychloroquine 23 (10.6%) and convalescent plasma 194 (6.9%) alone or in combination with other agents were the most frequently used interventions in published and registered RCTs, respectively. Most published RCTs have been conducted in Western Pacific Region (WPRO) (50 trials, 23.0%) including 45 trials from China. Also, a greater proportion of registered RCTs have been conducted in the Region of the Americas (PAHO) (885 trials, 31.6%) including 596 RCTs from the United States (U.S). Globally, 283 registered trials have been conducted to assess new developed vaccines for COVID or previously established for other disorders. CONCLUSION: The present study highlighted the wide range of potential therapeutic agents in published and registered COVID-19 clinical trials across a wide range of regions. However, it is urgently required to global coordination in order to conduct more well-designed trials and progress in discovering safe and effective treatments.