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Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Although the main cause of the onset and development of AD is not known yet, neuronal death due to pathologic changes such as amyloid-β (Aβ) deposition, tau aggregation, neuroinflammation, oxidative stress, and calcium dyshomeostasis are considered to be the main cause. At the present, there is no cure for this insidious disorder. However, accurate identification of molecular changes in AD can help provide new therapeutic goals. Caspases are a group of proteases which are known because of their role in cellular apoptosis. In addition, different caspases are involved in other cellular responses to the environment, such as induction of inflammation. Emerging evidence suggest that these proteases play a central role in AD pathophysiology due to their role in the processing of amyloid-β protein precursor, tau cleavage, and neuroinflammation. Therefore, it seems that targeting caspases may be a suitable therapeutic option to slow the progression of AD. This review focuses on the role of caspases in AD pathophysiology and introduce results from studies targeted caspases in different models of AD.

One of the main players in apoptosis during Alzheimer’s disease progression are different members of caspase family of proteases. The most well-known member of this family is caspase-3, in which alterations of its levels have been detected in samples from Alzheimer’s disease patients. There are numerous intracellular factors involved in regulation of cellular apoptosis through regulation of caspase-3 activity, the most important of which is the PI3K/AKT signaling pathway. This commentary tries to highlight the probable relations between PI3K/AKT signaling pathway and caspase-3 in Alzheimer’s disease.

Partial necrosis of skin flaps following plastic and reconstructive surgeries is one of the major problems in these medical interventions. This study was conducted to evaluate the beneficial effects of topiramate an anti-epileptic agent on ischemic random skin flaps.Twenty-four Wistar rats were provided and randomly divided into four experimental groups (control group and low-, intermediate- and high-dose treatment groups). A rat random-pattern skin flap model was performed in all groups, and animals in the low-, intermediate- and high-dose experimental groups were administered topiramate intraperitoneally at doses of 25, 50 and 100 mg/kg, respectively, 1 h before raising the flap and once daily for 7 consecutive days after the initial surgical procedure. Control rats received vehicle according to the same schedule. On postoperative day 7 the flap necrotic area was measured, and tissue samples were stained with hematoxylin and eosin for histological analysis. Furthermore, the oxidative stress in flap tissue was assessed by measuring the activity of superoxide dismutase (SOD), glutathione (GSH) level and the content of malondialdehyde (MDA).Treating animals with 50 and 100 mg/kg topiramate significantly decreased the necrotic flap areas as compared to the control group. Histological studies demonstrated that in intermediate and high dose topiramate groups the inflammatory cell numbers were attenuated and microvessel development were markedly increased. Furthermore, the MDA contents were significantly reduced and GSH levels were significantly increased in these groups as compared to the control group. However, the SOD activity was increased significantly only in high-dose group as compared to the control group.These findings indicated that topiramate in doses of 50 and 100 mg/kg increases random skin flap survival.This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the world's health systems for more than two years. This disease causes a high mortality rate followed by cytokine storm-induced oxidative stress and acute respiratory distress syndrome (ARDS). Therefore, many drugs have been considered with emphasis on their anti-inflammatory and antioxidant effects in controlling the consequences of SARS-CoV-2 infection. Icariin is a major bioactive pharmaceutical compound derived from Epimedium plants, which is known due to its anti-inflammatory and antioxidant effects. Additionally, the protective effects of icariin have been studied in different pathologies through modulating intracellular pathways. In addition to the potential effect of this compound on inflammation and oxidative stress caused by SARS-CoV-2 infection, it appears to interfere with intracellular pathways involved in viral entry into the cell. Therefore, this paper aims to review the molecular mechanisms of anti-inflammatory and antioxidant properties of icariin, and hypothesizes its potential to inhibit SARS-CoV-2 entry into host cells through modulating the intracellular pathways.

Ulcerative colitis is an intestinal inflammatory condition characterized by rise of inflammatory mediators’ production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which its anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis induced at the first day of study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed and colon tissues removed for further macroscopic, histopathologic, and biochemical analysis. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and up-regulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity.

Alzheimer’s disease (AD) is the most common neurodegenerative disease and the leading cause of dementia worldwide. Different pathologic changes have been introduced to be involved in its progression. Although amyloid-β (Aβ) deposition and tau hyperphosphorylation and aggregation are mainly considered the main characterizations of AD, several other processes are involved. In recent years, several other changes, including alterations in gut microbiota proportion and circadian rhythms, have been noticed due to their role in AD progression. However, the exact mechanism indicating the association between circadian rhythms and gut microbiota abundance has not been investigated yet. This paper aims to review the role of gut microbiota and circadian rhythm in AD pathophysiology and introduces a hypothesis to explain their association.

Topiramate is an anticonvulsant drug effective against a wide range of seizures and epilepsies. The present study was conducted to investigate the possible protective effect of topiramate on indomethacin-induced gastric mucosal damage in rats. The animals were randomly distributed into four experimental groups with 10 animals in each group. Group 1 was the control group received vehicle only (DMSO at 1:4 (w/v)), group 2 was the model group received indomethacin (50 mg/kg; i.p.), and groups 3 and 4 received topiramate (100 mg/kg; i.p.) and ranitidine (100 mg/kg; i.p.), respectively, 1 h before indomethacin (50 mg/kg; i.p.). The efficacy of topiramate was compared with ranitidine. Animals were euthanized 4 h after indomethacin administration, and gastric tissues were collected for macroscopical, histopathological, and biochemical analyses. The mucosal lesions in the gastric corpus were evaluated by pathological examinations. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestation, whereas topiramate pretreatment extensively ameliorated the gastric injuries. Topiramate pretreatment also reduced the contents of tissue malonaldehyde, enhanced ferric reducing antioxidant power value and glutathione levels, and increased the activity of superoxide dismutase, catalase, and glutathione peroxidase in gastric mucosa compared to the model group. Our results indicate that topiramate might possess a protective role against indomethacin-induced gastric ulcers by inhibition of oxidative stress in gastric tissue.

The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity.What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia.What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia.

In recent years, the association between the activity of platelets and risk of Alzheimer’s disease (AD) risk has been noticed in numerous studies. However, there in no investigations on the role of specific intracellular pathways to explain this connection. The phosphatidylinositol 3 kinase (PI3K)/AKT pathway is one of the main regulators of cell survival which regulates cellular responses to environmental changes. This pathway also regulates the activity of platelets, and its aberrant activity has been linked to platelet dysfunction in different pathologies. On the other hand, the PI3K/AKT pathway regulates amyloid-β (Aβ) production through regulation of amyloid-β protein precursor (AβPP), BACE-1, ADAMs, and γ-secretase. In addition, alterations in the activity of all of these factors in platelets has been shown in AD-related pathologies. Therefore, this paper aims to introduce the PI3K/AKT pathway as a molecular inducer of platelet dysfunction during aging and AD progression.

The current COVID-19 pandemic is one of the most devastating events in recent history. The respiratory effects of this disease include acute respiratory distress syndrome, systemic inflammation, cytokine storm, and pulmonary fibrosis. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is a peptide hormone secreted mainly by the stomach. Interestingly, ghrelin possesses promising antioxidant, anti-and inflammatory effects, making it an attractive agent to reduce the complications of the SARS-CoV-2. In addition, ghrelin exerts a wide range of immunomodulatory and anti-inflammatory effects and can mitigate the uncontrolled cytokine production responsible for acute lung injury by upregulating PPARγ and down-regulating NF-κB expression. Ghrelin has also been reported to enhance Nrf2 expression in inflammatory conditions which led to the suppression of oxidative stress. The current opinion summarizes the evidence for the possible pharmacological benefits of ghrelin in the therapeutic management of SARS-CoV-2 infection.

Rheumatoid arthritis (RA) is an autoimmune erosive disease leading to bone and cartilage destruction. It causes pain, inflammation, and swelling. Because of the severe adverse effects of chemical drugs, phytoremediation is taken to be considered nowadays. It is important to find out novel drug formulations and their mechanisms in rheumatoid arthritis to reduce patients suffering from this long-term disease. We suggest this hypothesis that Resveratrol (RSV) may act its anti-rheumatoid arthritis effects by STAT3/HIF-1/VEGF pathway for these reasons: (A) RSV exhibits anti-inflammatory properties, which can reduce inflammation of joints, (B) RSV reduces the level of pro-inflammatory cytokines accumulation, (C) RSV can suppress the expression of HIF-1 and VEGF genes and also inhibits STAT3 function. These molecules and their functions cause the disease progression of RA. Thus RSV can act as an anti-RA drug in this way, (D) According to previous findings, angiogenesis plays one of the main roles in RA and RSV inhibits angiogenesis via STAT3/HIF-1/VEGF pathway. By this explanation, RSV may perform its anti-RA function through this molecular pathway. PRACTICAL APPLICATIONS: Resveratrol (RSV) is a kind of stilbenoid that exhibits antioxidant, anti-inflammatory, and anti-angiogenesis activities by various molecular pathways. It exists in many plants like grapes, blueberries, etc. and it is the main component of red wine. It is a safe compound and it has beneficial effects on rheumatoid arthritis (RA). RSV decreases pain and helps ameliorate swollen joints which makes it a good candidate for RA patients, also it showed protective effects on osteoarthritis by reducing inflammation markers. We recommend the theory that RSV has therapeutic effects on RA via STAT3/HIF-1/VEGF molecular pathway and we investigate more information about it in this article. As this paper shows pharmacological and clinical documents about RSV in RA, it considers that RSV can ameliorate RA in STAT3/HIF-1/VEGF molecular pathway.

Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in the hippocampus, leading to severe impairment in behavior, learning, and memory functions. This study aimed to evaluate the neuroprotective effects of bisoprolol (biso) and vitamin E (vit E) treatment alone or in combination on cerebral ischemia/reperfusion (I/R) injury. A total of 30 male rats were divided randomly into five groups (n = 6), sham, I/R, I/R + biso, I/R + vit E, and I/R + biso+vit E. Cerebral I/R group underwent global ischemia by bilateral common carotid artery occlusion for 20 min. Treatment groups received drugs once daily intraperitoneally for 7 days before the I/R induction. Locomotive and cognitive behaviors were utilized by open-field and Morris water maze tests. After behavioral testing, the brain was removed and processed to evaluate cerebral infarct size, histopathologic changes, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) level. In I/R group tissue MDA and MPO levels and cerebral infarct size were significantly increased in comparison with the sham group. Furthermore, significant deficits were observed in locomotion and spatial memory after I/R. The areas of cerebral infarction, MPO, and MDA levels in biso, vit E, and combination group were significantly reduced compared with I/R group. Histopathological analysis demonstrated a significant reduction in leukocyte infiltration in all treated groups with the most profound reduction in the combination group. According to the behavioral tests, administration of biso and/or vit E protected locomotive ability and improved spatial memory after cerebral I/R. Our findings show that biso and vit E have beneficial effects against the I/R injury and due to their synergistic effects when administered in combination, may have a more pronounced protective effect on the cerebral I/R injury.

Purpose Hirsutism (ie, terminal hair growth on the face and body in a male-like pattern in women) is a common dermatological disorder in women, with psychosocial implications. Consequently, there is demand for finding novel pharmacological treatments and agents that can safely reduce hair growth. This study aimed to investigate the potential effect of topical acyclovir on hair growth in mice. Methods In this study, twenty -four female BALB/c mice were randomly divided into three groups in order to evaluate the hair growth-reducing effects of acyclovir (control group, vehicle group, and acyclovir group). Topical acyclovir 5% was applied on the shaved denuded skin of mice. Topical application onto the backs of the animals was performed twice daily for 28 consecutive days. The time (in days) required for hair growth initiation as well as completion of hair growth in dorsal skin of animals were recorded. On day 28, horizontally cut biopsy samples were removed and the numbers of hair follicles were counted, and the diameter of hair follicles was measured under high-field microscopy by a specialist blinded to the treatments. Results Hair growth initiation time was significantly increased with acyclovir, as compared to control and vehicle groups. The time required for complete hair growth in control and vehicle groups were 18±0.68 and 19±1.41 days, respectively ; however, the hair growth completion in acyclovir-treated animals was not observed at the end of the experiment . Furthermore, the length of hairs in treatment group was significantly shorter than the control group at the end of the study (P < 0.001). In histologic examination, the count and the diameter of hair follicles in deep subcutis were significantly decreased. Conclusion The results of this study, for the first time, showed that topical administration of acyclovir might have inhibitory effects on hair growth in experimental animals ; however, further studies are required to understand its mechanism.

COVID-19 is a rapidly spreading disease, causing a global pandemic. It is circulating in multiple countries and causing a series of respiratory infections. Due to the uncertain safety and efficacy of the vaccines and lack of specific medicines, it’s important to investigate new pharmacological procedures and find out new drugs that help us eradicate this pandemic. We suggest the hypothesis that Notopterol (NOT), the main Secondary metabolite of Notopterygium incisum Ting ex H.T (a common Chinese medicinal herb), may have the potential benefits on SARS-CoV2 infection for this reasons: (a) NOT exhibits anti-inflammatory, anticancer, and anti-angiogenic properties, (b) NOT indicates a significant reduction in cytokines and chemokines releasing including TNFa, IL-6, interferon-γ, which may decrease COVID-19 cytokine storm (c) NOT can suppress the expression of genes which leads to inflammation via Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway. It is exactly acting like tocilizumab, (an approved drug against COVID-19) and (d) Notopterygium incisum has antiviral activity against influenza virus, it can reduce the viral-induced oxidative stress. By these explanations, it is hopeful that NOT may be effective in COVID-19 infections which needs further investigations to examine Notopterol as a beneficial agent against the SARS-CoV2 infection.

Genistein is the simplest secondary metabolite in soybeans and belongs to a group of compounds called isoflavones. It is a phytoestrogen and it makes up more than 60% of soy isoflavones. Studies have shown the anti-inflammatory, anti-apoptotic, and anti-angiogenic effects of genistein in addition to its modulatory effects on steroidal hormone receptors. In this review, we discuss the pharmacologic and therapeutic effects of genistein on various diseases. PRACTICAL APPLICATIONS: In this review, we have discussed the therapeutic effects of genistein as the main constituent of soybeans on health conditions. Its antioxidant, anti-inflammatory, anti-apoptotic and, anti-angiogenic effects need more attention. The pharmacological properties of genistein make this natural isoflavone a potential treatment for various diseases such as postmenopausal symptoms, cancer, bone, brain, and heart diseases. Special emphasis should be given to it, resulting in using it in clinical as a safe, potent, and bioactive molecule.

Phosphine (PH3), from hydrolysis of magnesium, zinc, and aluminum phosphide (AlP), is a rodenticide and insecticide which is used to avoid losses of the agriculture products. However, using of this agent may affect the human health, in a way that poisoning with AlP has a high rate of mortality and morbidities. This study determined the ameliorative effects of metformin (MET) on AlP-induced hepato- and nephro-toxicity in Wistar rats. Male rats were randomly divided into four experimental groups. Group I was the control group received coconut oil by oral gavage, group II was the model group received AlP (12 mg/kg) distributed in coconut oil by oral gavage, group III received MET (200 mg/kg; i.p.), and group IV received MET (200 mg/kg; i.p.) 30 min after intoxication. After 24 h, the serum, liver and kidney tissues were collected for histopathological and biochemical investigations. The levels of kidney function markers, blood urea nitrogen and creatinine, and liver function markers, ALP, AST and ALT, in the plasma were increased significantly followed by AlP intoxication. The results revealed that phosphine causes a significant enhancement of lipid peroxidation, while decreases the activity of superoxide dismutase in both liver and kidney tissues. Furthermore, phosphine significantly induced the up-regulation of TNF-α and phosphorylation of NF-κB in target tissues. Overall, treatment with MET abolished aforementioned alterations resulted by AlP intoxication. Furthermore, histological evaluation indicated a deleterious effect of AlP on the liver and kidney tissues along with marked increase in kidney and liver injury scores, which is mitigated by MET administration. According to our results, although metformin could not bring the changes to the level of the control group, it was indicated that this drug might possess a protective effect against AlP-induced hepato and nephrotoxicity by inhibiting inflammatory responses and oxidative stress.

Neurodegenerative diseases are characterized by a progressive loss of neurons of the central nervous system (CNS) and serve as a major cause of morbidity, mortality and functional dependence especially among the elderly. Despite extensive research and development efforts, the success rate of clinical pipelines has been very limited. However, microRNAs (miRs) have been proved to be of crucial importance in regulating intracellular pathways for various pathologic conditions including those of a neurodegenerative nature. There is ample evidence of altered levels of various miRs in clinical samples of Alzheimer's disease and Parkinson's disease patients with potentially major clinical implications. In the current review, we aim to summarize the relevant literature on the role of miRs in the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD) as the two globally predominant neurodegenerative conditions.

COVID-19, caused by the SARS-CoV-2, has challenged the health care systems of the world. Although the pulmonary complications of the infection have received extensive attention, addressing the other complications (e.g., changes in androgen levels) could further provide a more efficient understanding of the disease, which might aid in combating it. Since the association between androgens and the expression and activity of SARS-CoV-2 receptors has been proven and anti-androgen-based therapies have been considered in this regard, addressing various aspects of androgen level changes can be constructive. The present paper examines the possible mechanisms of changes in androgen levels by the virus. It seems that the infection of the gonads by the SARS-CoV-2 could reduce the androgen levels by affecting different cellular pathways.

In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and has now spread worldwide. There are no specific drugs for the disease caused by this virus, coronavirus disease 2019 (COVID-19). Considering that new synthesized drugs cannot be applied immediately to patients, conventional drug in new use is a feasible solution. Chloroquine, remdesivir, favipiravir, lopinavir, ribavirin, and ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory, and bronchodilatory effects, has previously been shown to inhibit several viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases the levels of cyclic adenosine monophosphate, which in turn activates protein kinase, leading to a reduction in the synthesis of pro-inflammatory cytokines and immune cell migration. Here, we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 based on its interesting properties.

The current COVID‐19 pandemic is one of the most devastating events in recent history. In the lack of a specific treatment and vaccine for this novel infection, finding effective drugs against this infection is crucial. We suggest the hypothesis that crocin, the main carotenoid of saffron, has the potential to limit the progression and severity of the SARS‐CoV2 infection for several reasons: (a) crocin possesses powerful antioxidant properties, (b) crocin can alleviate the uncontrolled cytokine production responsible for acute lung injury, (c) crocin can upregulate PPARγ and downregulate NF‐κB expression which leads to a wide range of immunomodulatory and anti‐inflammatory effects, and (d) crocin can reduce the viral‐induced oxidative stress and downregulates ACE2 expression by activating Nrf2 pathway. We hope our hypothesis, corroborated by preclinical evidence, will inspire further targeted studies to test crocin as a beneficial drug against the SARS‐CoV2 infection. Practical applications Crocin is a natural antioxidant and the main active carotenoid components of saffron. We suggest the hypothesis that crocin has the potential to limit the progression and severity of the SARS‐CoV2 infection because of its antioxidant and anti‐inflammatory properties. Furthermore, this compound may prevent viral entry to host cells and reduce SARS‐CoV2‐induced lung injury. Therefore, we suggest further clinical studies on the effects of crocin against SARS‐Cov‐2 infection., Crocin can alleviate the uncontrolled cytokine production responsible for acute lung injuryCrocin with immunomodulatory and anti‐inflammatory effects and antioxidant properties has the potential to limit the progression and severity of the SARS‐CoV2 infectionCrocin may prevent viral entry to host cells and reduce SARS‐CoV2‐induced lung injury

Summary Introduction Testicular torsion is a common urologic emergency and one of the causes of infertility in males. Hence, prompt diagnosis and treatment are important to prevent testicular damages. It has been reported that memantine, a drug for Alzheimer's disease has anti-oxidative role against cerebral ischemic stroke and cardiac ischemia reperfusion. Objective In this experimental study, the effects of memantine on a testicular torsion injury in adolescent rat testis after ischemia/reperfusion (I/R) were evaluated. Study design Thirty-six adolescent rats were divided into three groups with 12 rats per group including sham-operated, T/D (torsion/detorsion) + vehicle, and T/D + memantine (10 mg/kg). Testicular torsion was induced for 2 h by rotating right testis 7200 in the clockwise direction. In treated group 30 min before detorsion, a single intraperitoneal dose of memantine was administered. After 4 h of reperfusion, orchiectomy was conducted and Histopathological and biochemical evaluations of testicular tissue samples were performed. Results The malondialdehyde level in the T/D group was significantly greater than in the sham operated group. Moreover, the testicular malondialdehyde values in the T/D + memantine group were significantly lower than in the T/D group. Also, significant decreases occurred in catalase and superoxide dismutase activities in the T/D group compared with sham operated group. These values were significantly greater in the memantine group than in the T/D group. Furthermore, after induction of T/D, histopathological evaluations also revealed severe testicular damages which were improved by memantine administration. Discussion Memantine prevented increases in oxidative stress markers and reductions of antioxidants during I/R injury in the current study. Subsequently the histologic injury was reduced in rats treated with memantine. The antioxidant characteristics of memantine and its protective effects have been shown in our study. Conclusion These results suggest that administration of memantine before detorsion prevents I/R cellular damage in testicular torsion. This drug probably acts through reduction of reactive oxygen species and support antioxidant enzyme systems. Download : Download high-res image (308KB) Download : Download full-size image Summary Figure . Administration of memantine before detorsion ameliorates the oxidative stress and decreases the histologic damage that occurs after testicular torsion.

The current COVID-19 is one of the deadliest pandemics in recent decades. In the lack of a specific treatment for this novel infection, knowing the role of cell signaling pathways in the pathogenesis of this infection could be useful in finding effective drugs against this disease. The mammalian or mechanistic target of rapamycin (mTOR) is an important cell signaling pathway that has important role in the regulation of cell growth, protein synthesis, and metabolism in reactance to upstream signals in both pathological and normal physiological conditions. Recently, some researchers have suggested the therapeutic potential of mTOR inhibitors such as rapamycin against COVID-19. However, it is important to consider the role of activation of this pathway in controlling immune system response against viral activity in drug repositioning of rapamycin and other mTOR inhibitors in SARS-CoV-2 infection.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. The association between AD and other diseases such as diabetes is well-studied. In parallel, potential disease-modifying effects of therapeutic agents used for diabetes have been investigated in the context AD of. Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin's potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-β (Aβ) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models. In this review, we summarize the relevant scientific literature on the effects of metformin on various aspects of AD pathophysiology.

A recent outbreak of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in Wuhan, China, at the end of 2019 and then spread rapidly all over the world. However, there are no specific antiviral therapies for COVID-19, using the agents which approved or in development for other viral infections is one of the potentially quickest ways to find treatment for this new viral infection. Favipiravir is an effective agent that acts as a nucleotide analog that selectively inhibits the viral RNA dependent RNA polymerase or causes lethal mutagenesis upon incorporation into the virus RNA. In view of recent studies and discussion on favipiravir, in this mini review we aimed to summarize the clinical trials studying the efficacy and safety of favipiravir in patients with COVID-19.

Azithromycin, a member of the macrolide family of antibiotics, is commonly used to treat respiratory bacterial infections. Nevertheless, multiple pharmacological effects of the drug have been revealed in several investigations. Conceivably, the immunomodulatory properties of azithromycin are among its critical features, leading to its application in treating inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Additionally, azithromycin may directly inhibit viral load as well as its replication, or it could demonstrate indirect inhibitory impacts that might be associated with the expression of antiviral genes. Currently, coronavirus disease 2019 (COVID-19) is an extra urgent issue affecting the entire world, and it is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress syndrome (ARDS), which is associated with hyper inflammation due to cytokine release, is among the leading causes of death in COVID-19 patients with critical conditions. The present paper aims to review the immunomodulatory and antiviral properties of azithromycin as well as its potential clinical applications in the management of COVID-19 patients.

The imbalance of Th17/Treg cells has been recently suggested as a new risk factors for recurrent implantation failure (RIF). Furthermore Th17/Treg cells are involved in immune regulation in peripheral blood and endometrial tissue of patients with RIF. In this research, we investigated the effects of Hydroxychloroquine (HCQ) on the level and function of Th17 and Treg cells in women with RIF. It may be possible to improve pregnancy outcomes by modulating high cytokine levels.Women with RIF received oral HCQ (Our results demonstrated that the administration of HCQ in RIF women with immune cell disorders during pregnancy could affect the Th17/Treg ratio and enhance Treg and diminish Th17 responses which may be associated with successful pregnancy outcomes. However, significant difference in pregnancy outcomes was not observed in the present study.

Gastrointestinal cancers are one of the most common types of cancer that have high annual mortality; therefore, identification and introduction of safe drugs in the control and prevention of these cancers are of particular importance. Metformin, a lipophilic biguanide, is the most commonly prescribed agent for type 2 diabetes management. In addition to its great effects on lowering the blood glucose concentrations, the anti-cancer properties of this drug have been reported in many types of cancers such as gastrointestinal cancers. Hence the effects of this agent as a safe drug on the reduction of gastrointestinal cancer risk and suppression of these types of cancers have been studied in different clinical trials. Furthermore, the proposed mechanisms of metformin in preventing the growth of these cancers have been investigated in several studies. In this review, we discuss recent advances in elucidating the molecular mechanisms that are relevant for metformin use in gastrointestinal cancer treatment.

Testicular torsion is a common urologic emergency and one of the causes of genital injury in males. Hence, early diagnosis and treatment are necessary to prevent testicular damage and infertility. It has been proved that topiramate (TPM) a medication used to treat epilepsy and prevent migraines has anti-inflammatory and anti-oxidative effects. Therefore, this study was designed to determine the influence of TPM on ischemia/reperfusion injury following testicular torsion/detorsion (T/D). Thirty-six male Wistar rats were divided into three groups (n = 12 for each group) including sham operated, T/D + vehicle, T/D + TPM(100 mg/kg, 30 min before detorsion). Testicular torsion was induced for 1 h by rotating right testis 7200 in the clockwise direction. After 5 h of reperfusion the testis was removed and histological changes and biochemical markers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and levels of malondialdehyde (MDA) and reduced glutathione (GSH) were evaluated. MDA level significantly increased and GSH level significantly decreased after T/D compared to the sham group (p

Purpose Hirsutism (ie, terminal hair growth on the face and body in a male-like pattern in women) is a common dermatological disorder in women, with psychosocial implications. Consequently, there is demand for finding novel pharmacological treatments and agents that can safely reduce hair growth. This study aimed to investigate the potential effect of topical acyclovir on hair growth in mice. Methods In this study, twenty -four female BALB/c mice were randomly divided into three groups in order to evaluate the hair growth-reducing effects of acyclovir (control group, vehicle group, and acyclovir group). Topical acyclovir 5% was applied on the shaved denuded skin of mice. Topical application onto the backs of the animals was performed twice daily for 28 consecutive days. The time (in days) required for hair growth initiation as well as completion of hair growth in dorsal skin of animals were recorded. On day 28, horizontally cut biopsy samples were removed and the numbers of hair follicles were counted, and the diameter of hair follicles was measured under high-field microscopy by a specialist blinded to the treatments. Results Hair growth initiation time was significantly increased with acyclovir, as compared to control and vehicle groups. The time required for complete hair growth in control and vehicle groups were 18±0.68 and 19±1.41 days, respectively ; however, the hair growth completion in acyclovir-treated animals was not observed at the end of the experiment . Furthermore, the length of hairs in treatment group was significantly shorter than the control group at the end of the study (P < 0.001). In histologic examination, the count and the diameter of hair follicles in deep subcutis were significantly decreased. Conclusion The results of this study, for the first time, showed that topical administration of acyclovir might have inhibitory effects on hair growth in experimental animals ; however, further studies are required to understand its mechanism.

In this study, we investigated the potential of thymol and its mode of action to protect against the titanium dioxide (TiO2) nanoparticle–induced testicular damage. Twenty-four rats were randomly divided into four groups: control group, TiO2 (100 mg/kg BW/day) group, TiO2 + thymol (10 mg/kg BW/day) group, and TiO2 + thymol (30 mg/kg BW/day) group. With the exception of the control group, all animals received orally TiO2 nanoparticles for 60 days. In treatment groups, animals were given orally thymol 1 h before TiO2 nanoparticles. Epididymal sperm parameters, testicular histopathology, and spermatogenesis assessments were performed for evaluation of the TiO2 and thymol effects on the testis. Furthermore, antioxidative enzyme activities such as catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA), glutathione (GSH) levels and ferric-reducing antioxidant power (FRAP) value were measured. Intragastric administration of TiO2 for 60 consecutive days caused a significant decrease in sperm quality, widespread histopathological alteration, and significantly induced oxidative stress as manifested by elevated MDA levels and a remarkable decline in antioxidant enzyme activities such as CAT, SOD, and GPx, and also FRAP and GSH levels in testis tissue. Nearly all of these alterations were significantly ameliorated in the groups that orally received thymol before TiO2 nanoparticles administration. The results of this study demonstrated that thymol improved the spermatogenesis defects induced by TiO2 nanoparticles in rats in a dose-dependent manner by protecting the testes against the testicular toxicity. Reduction in TiO2 nanoparticle–induced oxidative stress may have a major role in this protective effect.

Humans are usually exposed to multiple pesticides in real life, but little is known as yet about the safety of low-dose pesticides mixtures. This study was conducted to evaluate the effects of long-term exposure to very low doses of pesticide mixtures on biochemical, histological, and neurobehavioral alterations in the rat model. For 90 days, four groups of male Wistar rats were given a mixture of five pesticides (in drinking water) in doses of 0, 0.25, 1 and 5 times the legally permitted levels (mg/kg body weight/day). After three-month exposure, the neurobehavioral effects of pesticide mixtures were evaluated by the Morris water maze, elevated plus maze and the open field tests. Then the biochemical and histopathological alterations in the hippocampus of studied animals were evaluated. Results showed that long-term exposure to a combination of five pesticides affected the nervous system in dose-dependent manner. As expected, nearly all of the parameters determined in this study were adversely changed in the high dose group. Exposure to medium dose (permitted level of pesticides mixture) was also able to induce oxidative stress and impaired memory and learning ability, although not all parameters were significantly changed in this group. It means that pesticides may behave differently when mixed. Interestingly, the administration of low doses of these chemicals induced an adaptive response by stimulating the redox system. In conclusion, it seems that the prolonged exposure to pesticide mixtures may cause adverse neurobehavioral effects, even at permitted levels.

Testicular torsion/detorsion (T/D) is an inflammatory problem in men genital system with infertility effects. Cyclosporine A (CsA) as an immunosuppressant medication, exerts anti-inflammatory properties in tissue injuries. We sought to compare the efficacy of 3 doses of CsA on oxidative stress, apoptosis and epididymal sperm quality after ipsilateral testicular T/D.96 mature male rats were divided into six groups 16 each in: Control group (Group1), Sham operated (Group2), In rest groups, the right testis was twisted 720° in a clockwise direction for 1 h; T/D + 0.1% dimethylsulfoxide) DMSO((Group3), and in groups 4-6; CsA were administered 1, 5, and 10 mg/kg, intravenously (iv) 30 and 90 min after torsion, respectively.Tissue malondialdehyde (MDA) level and caspase-3 activity increased and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities decreased in compared with control group 4 h after detorsion (p .001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by determining mean of seminiferous tubules diameters (MSTD) and TUNEL assay. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of animals.Pre- and post-reperfusion CsA diminished MDA and caspase-3levels and normalized antioxidant enzymes activities. Germ cell apoptosis was significantly reduced, as well as, MSTD and long-term sperm insults were improved. Inhibition of mitochondrial permeability transition pore opening is suggested mechanism for cell protection against testicular T/D insults.