A three month old infant with severe respiratory distress.

This case report discusses the diagnostic challenge of congenital lobar emphysema (CLE) in a three-month old infant with severe respiratory distress. The infant was initially misdiagnosed and managed as a case of pneumothorax. This case highlights the importance of CT scans as a diagnostic tool for early diagnosis and lifesaving management of CLE. It also signifies the need for adequate funds and infrastructure in the health care system especially in rural areas of developing countries like Pakistan.

Inhibition of Silver Diamine Fluoride-induced Tooth Discoloration by Using Natural Antioxidant: In Vitro Study.

AIM: Silver diamine fluoride (SDF) is a well-known caries preventive aid capable of arresting carious lesions and preventing secondary caries formation. Despite having the caries prevention potential, the clinical use of SDF is limited due to the tooth discoloration caused by SDF. The objective of this study was to evaluate the efficiency of natural antioxidants to inhibit SDF-induced tooth discoloration. MATERIALS AND METHODS: A total of 32 bovine teeth were polished to create a 6 mm circular window on the middle 1/3 (for enamel) or on the cervical 1/3 (for dentin) of the labial surface. Specimens were treated either with SDF alone or SDF followed by ascorbic acid (AA)/alpha lipoic acid (ALA)/7th generation bonding materials. The color parameters Lightness (L*), Chroma (C*), and Hue (H*) of the tooth window were measured at pretreatment, 1-hour, 1-week, and 1-month posttreatment using a digital color chromometer. RESULTS: Repeated measure ANOVA showed a significant tooth color alteration at 1-hour posttreatment. The L* and H* values dropped and C* value elevated significantly in 1-hour posttreatment measurement. All experimental groups showed significant tooth color alteration after treatment (p < 0.05) and were unable to reverse the discoloration even after 1-month period except the ALA group which did not show any significant (p > 0.05) color alteration compared with the pretreatment value. CONCLUSIONS: Within the limitation of the in vitro model and according to the results of this study, it can be concluded that ALA has the potential to prevent SDF-induced tooth discoloration; however, AA was unable to prevent the discoloration. CLINICAL SIGNIFICANCE: SDF induces discoloration of enamel and dentin can be reversed by applying Alpha lipoic acid immediacy after SDF application.

Auricular cartilage regeneration using different types of mesenchymal stem cells in rabbits.

BACKGROUND: Cartilaginous disorders comprise a wide range of diseases that affect normal joint movement, ear and nose shape; and they have great social and economic impact. Mesenchymal stem cells (MSCs) provide a promising regeneration alternative for treatment of degenerative cartilaginous disorders. This study aimed to compare therapeutic potential of different types of laser activated MSCs to promote auricular cartilage regeneration. Twelve adult rabbit allocated equally in four groups, all animals received a surgical mid auricular cartilage defect in one ear; Group I (Positive control) injected sub-perichondrially with phosphate-buffered saline (PBS), Group II (ADMSC-transplanted group) injected adipose-derived MSCs (ADMSCs), Group III (BMMSCs-transplanted group) received bone marrow-derived MSCs (BMMSCs), and Group IV (EMSC-transplanted group) received ear MSCs (EMSCs) in the defected ear. The auricular defect was analyzed morphologically, histopathologically and immunohistochemically after 4 weeks. In addition, a quantitative real-time polymerase chain reaction was used to examine expression of the collagen type II (Col II) and aggrecan as cartilage growth factors. RESULTS: The auricles of all treatments appeared completely healed with smooth surfaces and similar tissue color. Histopathologically, defective areas of control positive group, ADMSCs and EMSCs treated groups experienced a small area of immature cartilage. While BMMSCs treated group exhibited typical features of new cartilage formation with mature chondrocytes inside their lacunae and dense extracellular matrix (ECM). In addition, BMMSC treated group showed a positive reaction to Masson's trichrome and orcein stains. In contrary, control positive, ADMSC and EMSC groups revealed faint staining with Masson's trichrome and Orcein. Immunohistochemically, there was an intense positive S100 expression in BMMSCs (with a significant increase of area percentage + 21.89 (P < 0.05), a moderate reaction in EMSCs (with an area percentage + 17.97, and a mild reaction in the control group and ADMSCs (area percentages + 8.02 and + 11.37, respectively). The expression of relative col II and aggrecan was substantially highest in BMMSCs (± 0.91 and ± 0.89, respectively). While, Control positive, ADMSCs and EMSCs groups recorded (± 0.41: ± 0.21, ± 0.6: ± 0.44, ± 0.61: ± 0.63) respectively. CONCLUSION: BMMSCs showed the highest chondrogenic potential compared to ADMSCs and EMSCs and should be considered the first choice in treatment of cartilaginous degenerative disorders.

Timely Postpartum Visits for Low-Income Women: A Health System and Medicaid Payer Partnership.

A health care system and a Medicaid payer partnered to develop an educational intervention and payment redesign program to improve timely postpartum visits for low-income, high-risk mothers in New York City between April 2015 and October 2016. The timely postpartum visit rate was higher for 363 mothers continuously enrolled in the program than for a control group matched by propensity score (67% [243/363] and 56% [407/726], respectively; P < .001). An innovative partnership between a health care system and Medicaid payer improved access to health care services and community resources for high-risk mothers.

Genomic analysis of methicillin-resistant Staphylococcus aureus strain SO-1977 from Sudan.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is known as a leading cause of morbidity and mortality. Investigation of the MRSA's virulence and resistance mechanisms is a continuing concern toward controlling such burdens through using high throughput whole Genome Sequencing (WGS) and molecular diagnostic assays. The objective of the present study is to perform whole-genome sequencing of MRSA isolated from Sudan using Illumina Next Generation Sequencing (NGS) platform. RESULTS: The genome of MRSA strain SO-1977 consists of 2,827,644 bp with 32.8% G + C, 59 RNAs and 2629 predicted coding sequences (CDSs). The genome has 26 systems, one of which is the major class in the disease virulence and defence. A total of 83 genes were annotated to virulence disease and defence category some of these genes coding as functional proteins. Based on genome analysis, it is speculated that the SO-1977 strain has resistant genes to Teicoplanin, Fluoroquinolones, Quinolone, Cephamycins, Tetracycline, Acriflavin and Carbapenems. The results revealed that the SO-1977, strain isolated from Sudan has a wide range of antibiotic resistance compared to related strains. CONCLUSION: The study reports for the first time the whole genome sequence of Sudan MRSA isolates. The release of the genome sequence of the strain SO-1977 will avail MRSA in public databases for further investigations on the evolution of resistant mechanism and dissemination of the -resistant genes of MRSA.

Positive Deviance to Address Health Equity in Quality and Safety in Obstetrics.

Racial/ethnic disparities persist in obstetrical outcomes. In this paper, we ask how research in obstetrical quality can go beyond a purely quantitative approach to tackle the challenge of health inequity in quality and safety. This overview debriefs the use of positive deviance and mixed methods in others areas of medicine, describes the shortcomings of quantitative methods in obstetrics and presents qualitative studies carried out in obstetrics as well as the insights provided by this method. The article concludes by proposing positive deviance as a mixed methods approach to generate new knowledge for addressing racial and ethnic disparities in maternal outcomes.

Computational and biochemical studies of isothiocyanates as inhibitors of proteasomal cysteine deubiquitinases in human cancer cells.

Isothiocyanates (ITCs) are natural chemoprotective products found abundantly in cruciferous vegetables. However, the cancer-relevant targets and molecular mechanisms of ITCs remain unclear. We hypothesize that ITCs, as electrophiles, can interact with the catalytic triads (CYS, HIS, and ASP) of the proteasomal cysteine deubiquitinases USP14 and UCHL5, ultimately inhibiting their activities. In the current study, we exploited this possibility by performing both computational docking and biochemical validation assays using human breast and prostate cancer cell models. Docking results suggest that benzyl isothiocyanate, phenethyl isothiocyanate, and DL-sulforaphane are more potent inhibitors of UCHL5 than USP14, and these ITCs could interact with the catalytic triads of UCHL5 and USP14. Indeed, ubiquitin vinyl sulfone assay confirmed the inhibitory activity of each ITC on the ubiquitin-binding activity of UCHL5 and USP14. We also found that inhibition of USP-14 and UCHL5 activities by the ITCs caused increased levels of USP14 and UCHL5 proteins, but not the third 19S-deubiquitinating enzyme (DUB), POH1/RPN11, suggesting feedback loop activation and further supporting that ITCs are inhibitors of proteasomal cysteine DUBs. Associated with DUB inhibition by ITCs, ubiquitinated proteins were significantly increased, accompanied with induction of apoptosis, inhibition of proliferation and suppression of cell invasion. Our findings of ITCs as proteasomal cysteine DUB inhibitors should provide insightful information for designing, discovering and developing potent, specific 19S-DUB inhibitors for cancer therapies.

Genome-wide identification and characterization of NB-ARC resistant genes in wheat (Triticum aestivum L.) and their expression during leaf rust infection.

KEY MESSAGE: NB-ARC domain-containing resistance genes from the wheat genome were identified, characterized and localized on chromosome arms that displayed differential yet positive response during incompatible and compatible leaf rust interactions. Wheat (Triticum aestivum L.) is an important cereal crop; however, its production is affected severely by numerous diseases including rusts. An efficient, cost-effective and ecologically viable approach to control pathogens is through host resistance. In wheat, high numbers of resistance loci are present but only few have been identified and cloned. A comprehensive analysis of the NB-ARC-containing genes in complete wheat genome was accomplished in this study. Complete NB-ARC encoding genes were mined from the Ensembl Plants database to predict 604 NB-ARC containing sequences using the HMM approach. Genome-wide analysis of orthologous clusters in the NB-ARC-containing sequences of wheat and other members of the Poaceae family revealed maximum homology with Oryza sativa indica and Brachypodium distachyon. The identification of overlap between orthologous clusters enabled the elucidation of the function and evolution of resistance proteins. The distributions of the NB-ARC domain-containing sequences were found to be balanced among the three wheat sub-genomes. Wheat chromosome arms 4AL and 7BL had the most NB-ARC domain-containing contigs. The spatio-temporal expression profiling studies exemplified the positive role of these genes in resistant and susceptible wheat plants during incompatible and compatible interaction in response to the leaf rust pathogen Puccinia triticina. Two NB-ARC domain-containing sequences were modelled in silico, cloned and sequenced to analyze their fine structures. The data obtained in this study will augment isolation, characterization and application NB-ARC resistance genes in marker-assisted selection based breeding programs for improving rust resistance in wheat.

Plausibility of natural immunomodulators in the treatment of COVID-19-A comprehensive analysis and future recommendations.

The COVID-19 pandemic has inflicted millions of deaths worldwide. Despite the availability of several vaccines and some special drugs approved for emergency use to prevent or treat this disease still, there is a huge concern regarding their effectiveness, adverse effects, and most importantly, their efficacy against the new variants. A cascade of immune-inflammatory responses is involved with the pathogenesis and severe complications with COVID-19. People with dysfunctional and compromised immune systems display severe complications, including acute respiratory distress syndrome, sepsis, multiple organ failure etc., when they get infected with the SARS-CoV-2 virus. Plant-derived natural immune-suppressant compounds, such as resveratrol, quercetin, curcumin, berberine, luteolin, etc., have been reported to inhibit pro-inflammatory cytokines and chemokines. Therefore, natural products with immunomodulatory and anti-inflammatory potential could be plausible targets to treat this contagious disease. This review aims to delineate the clinical trials status and outcomes of natural compounds with immunomodulatory potential in COVID-19 patients along with the outcomes of their in-vivo studies. In clinical trials several natural immunomodulators resulted in significant improvement of COVID-19 patients by diminishing COVID-19 symptoms such as fever, cough, sore throat, and breathlessness. Most importantly, they reduced the duration of hospitalization and the need for supplemental oxygen therapy, improved clinical outcomes in patients with COVID-19, especially weakness, and eliminated acute lung injury and acute respiratory distress syndrome. This paper also discusses many potent natural immunomodulators yet to undergo clinical trials. In-vivo studies with natural immunomodulators demonstrated reduction of a wide range of proinflammatory cytokines. Natural immunomodulators that were found effective, safe, and well tolerated in small-scale clinical trials are warranted to undergo large-scale trials to be used as drugs to treat COVID-19 infections. Alongside, compounds yet to test clinically must undergo clinical trials to find their effectiveness and safety in the treatment of COVID-19 patients.

Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress.

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice. Methodology: SPS was induced by restraining animals for 2 h, followed by 20 min of forced swim, recuperation for 15 min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60 mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels. Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice. Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.

Effects of 1-methyl-1, 2, 3, 4-tetrahydroisoquinoline on a diabetic neuropathic pain model.

Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, contributing towards poor quality of life, amputation risk, and increased mortality. The available therapies for diabetic neuropathic pain (DPN) have limitations in terms of efficacy, tolerability and patient compliance. Dysfunction in the peripheral and central monoaminergic system has been evidenced in various types of neuropathic and acute pain. The objective of the present study was to investigate 1-methyl 1, 2, 3, 4-tetrahydroisoquinoline (1MeTIQ), an endogenous amine found in human brain with a known neuroprotective profile, in a model of streptozotocin (STZ) induced neuropathic pain. Methods: Diabetic neuropathy in male BALB/c mice was induced by intraperitoneal injection of a single dose of STZ (200 mg/kg). Upon development of DPN after 4 weeks, mice were investigated for mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test). Ondansetron (1.0 mg/kg i.p.), naloxone (3.0 mg/kg i.p.) and yohimbine (2.0 mg/kg i.p.) were used to elucidate the possible mechanism involved. Postmortem frontal cortical, striatal and hippocampal tissues were dissected and evaluated for changes in levels of dopamine, noradrenaline and serotonin using High-Performance Liquid Chromatography (HPLC) with UV detection. Results: Acute administration of 1MeTIQ (15-45 mg/kg i.p.) reversed streptozotocin-induced diabetic neuropathic static mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test), these outcomes being comparable to standard gabapentin. Furthermore, HPLC analysis revealed that STZ-diabetic mice expressed lower concentrations of serotonin in all three brain regions examined, while dopamine was diminished in the striatum and 1MeTIQ reversed all these neurotransmitter modifications. These findings suggest that the antihyperalgesic/antiallodynic activity of 1MeTIQ may be mediated in part via supraspinal opioidergic and monoaminergic modulation since they were naloxone, yohimbine and ondansetron reversible. Conclusion: It was also concluded that acute treatment with 1MeTIQ ameliorated STZ-induced mechanical allodynia and thermal hyperalgesia and restored brain regionally altered serotonin and dopamine concentrations which signify a potential for 1MeTIQ in the management of DPN.

Fraxetin attenuates disrupted behavioral and central neurochemical activity in a model of chronic unpredictable stress.

Purpose: Chronic unpredictable stress (CUS) induces long-term neuronal and synaptic plasticity with a neurohormonal disbalance leading to the development of co-existing anxiety, depression, and cognitive decline. The side effects and delayed onset of current clinically used antidepressants has prompted a quest for antidepressants with minimum drawbacks. Fraxetin is a natural coumarin derivative with documented antioxidant and neuroprotective activity though its effects on stress are unknown. This study therefore aimed to investigate any possible acute effect of fraxetin in behavioral tests including a CUS paradigm in correlation with brain regional neurochemical changes. Methods: Mice were subjected to a series of mild stressors for 14 days to induce CUS. Furthermore, behavioral performance in the open field test, forced swim test (FST), Y-maze and elevated plus-maze were evaluated. Postmortem frontal cortical, hippocampal and striatal tissues were analyzed via high-performance liquid chromatography (HPLC) for neurochemical changes. Result: Acute administration of fraxetin (20-60 mg/kg, orally) decreased depression-like behavior in the FST and behavioral anxiety in both the open field test and elevated plus-maze. Memory deficits induced during the CUS paradigm were markedly improved as reflected by enhanced Y maze performance. Concurrent biochemical and neurochemical analyses revealed that only the two higher fraxetin doses decreased elevated serum corticosterone levels while diminished serotonin levels in the frontal cortex, striatum and hippocampus were reversed, though noradrenaline was only raised in the striatum. Concomitantly, dopamine levels were restored by fraxetin at the highest dose exclusively in the frontal cortex. Conclusion: Acute treatment with fraxetin attenuated CUS-induced behavioral deficits, ameliorated the increased corticosterone level and restored altered regional neurotransmitter levels and this may indicate a potential application of fraxetin in the management of anxiety and depression modeled by CUS. However, further studies are warranted regarding the chronic effects of fraxetin behaviorally and neurochemically.

Histopathological, Immunohistochemical, And Molecular Alterations In Brain Tissue And Submandibular Salivary Gland Of Atrazine-Induced Toxicity In Male Rats.

Atrazine (ATZ) is herbicide that has been widely used for different crops. This extensive use has resulted in severe deleterious effects in different species. In this work, we investigated the potentially harmful effect of atrazine herbicide on the brain and submandibular salivary gland. Our investigation was carried out on 20 adult male albino rats that were equally divided into two groups. The first group received distilled water as control, while the second group received ATZ at 200 mg/kg body weight/ day via stomach gavage for 30 successive days of the experiment; the oral LD50 for ATZ is 3090 mg/kg. Our findings revealed the ability of ATZ to cause damage to the cerebrum, hippocampus, and submandibular salivary gland. This damage resulted from the induced oxidative stress, which was indicated by a significant elevation in malondialdehyde (MDA) concentration, DNA fragmentation, tumor necrotic factor-alpha (TNF-α) expression, with a significant decrease in reduced glutathione (GSH) level and reduction of B cell lymphoma 2 (BCL2), dopamine receptor D1 (Drd1), cAMP-responsive element-binding protein 1 (Creb1) genes expression after ATZ exposure. Moreover, degeneration of cells, cytoplasmic vacuolation, congestion of blood vessels, a strong immune reaction to caspase 3, and negligible immune expression of a glial fibrillary acidic protein (GFAP) were also noticed in the ATZ-treated group. We concluded that ATZ induces oxidative stress and has a toxic and apoptotic effects on the cerebrum, hippocampus, and salivary gland of adult male albino rats.

Oxidative stress, apoptosis and histopathological alterations in brain stem and diencephalon induced by subacute exposure to fipronil in albino rats.

Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress-induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.

Exposure to Polystyrene nanoparticles induces liver damage in rat via induction of oxidative stress and hepatocyte apoptosis.

Plastic products are widely used in different applications. Thus, exposure of human and other organisms to these products may affect their biological system. The current study was conducted to investigate the potential deleterious effect of Polysterene nanoparticles (PS-NPs) on the liver and to state the cellular and molecular mechanisms associated with exposure to PS-NPs.30 male rats were divided randomly and equally into 3 groups; control (distilled water), low dose (3 mg/kg/day) and high dose (10 mg/kg/day) exposed group via oral gavage for 5 successive weeks. PS-NPs caused elevation in ALT, AST and MDA, upregulation of apoptosis-related genes and significant decrease in GSH and mRNA expression for antioxidant-related genes (Nrf-2 and GPx). Moreover, alterations in hepatic tissue architecture and positive caspase-3 expression was noticed in a dose- dependent manner. Collectively, PS-NPs can induce hepatoxicity in rats in a dose dependent manner, so the health risk of PS-NPs should not be ignored.

Histopathological, immunohistochemical, and molecular investigation of atrazine toxic effect on some organs of adult male albino rats with a screening of Acacia nilotica as a protective trial.

Atrazine (ATZ) is a widely used herbicide; however, it has deleterious effects. The current study aimed to investigate the potential toxic effect of ATZ as a neuroendocrine disruptor on the cerebellum and thyroid gland and on the liver as a detoxifying organ. We examined the ability of ATZ to induce oxidative stress and subsequent apoptosis in these organs. Moreover, we investigated the potential protective effect of Acacia nilotica, because of its potent antioxidant activity. Thus, our study was carried out on 40 adult male albino rats that were divided equally into 4 groups (10 rats/each group). The first group received distilled water, while the second group received ATZ dissolved in corn oil at 200 mg/kg body weight/day by stomach gavage. The third group was treated orally by ATZ (200 mg/kg body weight/day) plus Acacia nilotica (400 mg/kg/day). Group IV received Acacia nilotica only at a dose (400 mg/kg/day). After successive 30 days of the experiment, blood and tissue samples were collected from all groups. Our findings revealed the ability of ATZ to induce toxic effects was observed microscopically in the form of degenerated neurons and vacuolated neuropil of the cerebellum, degenerated hepatocytes, and vacuolation of the follicular cells of the thyroid gland. Furthermore, ATZ significantly elevated AST, ALT, and ALP serum levels and TB concentration, while decreased GSH. DNA fragmentation% and activated caspase-3 expression significantly increased after ATZ exposure. Interestingly, Acacia nilotica administration was able to partially protect the examined organs against the toxic effect of ATZ exposure.

Repurposing of Metformin for Cancer Therapy: Updated Patent and Literature Review.

BACKGROUND: Over recent years, there has been an increasing focus on the repurposing of existing, well-known medications for new, novel usage. One such drug is metformin, typically utilized in the management of diabetes, which demonstrates a positive relationship between its administration and lower cancer morbidity and mortality. Based on this finding, numerous studies and clinical trials have been conducted to examine the potential usage of metformin as an anticancer agent. OBJECTIVE: This article aims to summarize metformin's anticancer effects through reviewing its literatures and patents, with a focus on its potential to be repurposed for cancer therapy. METHODS: Various databases were examined using keywords, 'Metformin' and 'Cancer'. Research articles were collected through the PubMed database, clinical trials were obtained from the Clinical Trials database, and patents were collected through the Google Patents database. RESULTS: Metformin shows antineoplastic activity in various models. These anticancer properties appear to synergize with existing chemotherapeutics, which allows a reduction in drug dosage without losing potency while minimizing adverse effects. Numerous patents on metformin have been filed which claim various combination therapies, delivery methods, and uses for cancer therapy, displaying an increasing interest in metformin's anticancer potential. CONCLUSION: Preclinical studies, along with early phase clinical trials, have examined the antitumor properties of metformin on a variety of cancers. Metformin's anticancer effects are well documented, demonstrating a great promise in improving current cancer therapies. However, there is a significant lack of late phase clinical trials, specifically those involving nondiabetic cancer patients, and therefore further research in this area is required.

Correction: Knowledge, attitude, and perceptions towards the 2019 Coronavirus Pandemic: A bi-national survey in Africa.

[This corrects the article DOI: 10.1371/journal.pone.0236918.].

Evaluation of the effect of methotrexate on the hippocampus, cerebellum, liver, and kidneys of adult male albino rat: Histopathological, immunohistochemical and biochemical studies.

Methotrexate (MTX) has been used for treatment of autoimmune diseases, inflammatory disorders as rheumatic arthritis, and different types of cancers. However, it has shown adverse effects on vital organs. The current study was conducted to investigate the toxic effect of MTX on the hippocampus, cerebellum, liver and kidneys of adult male albino rats. MTX was injected weekly at 5 mg/kg body weight via I/P injection for 6 weeks. At the end of the experiment, histopathological, immunohistochemical and biochemical evaluation were performed on the hippocampus, cerebellum, liver, and kidney tissues of the sacrificed rats. We observed that methotrexate induced neural tissue damage in the hippocampus and cerebellum, degeneration of hepatocytes, congestion of the central vein and blood sinusoids of the liver, distortion in the renal corpuscles and necrosis of the renal tubule. Immunohistochemical findings revealed strong positive expression of Caspase-3, PCNA and GFAP. Biochemical studies revealed significant elevation in the serum levels of AST and ALT, in addition to high serum concentrations of creatinine and urea. Also, MTX injection increased MDA, while it decreased GSH, SOD and AChE levels. We conclude the ability of MTX to induce oxidative stress that results into apoptosis and tissue injury, leading to neurotoxicity, hepatotoxicity, and nephrotoxicity.