Gut microbiota in neurological diseases: Melatonin plays an important regulatory role.

Melatonin is a highly conserved molecule produced in the human pineal gland as a hormone. It is known for its essential biological effects, such as antioxidant activity, circadian rhythm regulator, and immunomodulatory effects. The gut is one of the primary known sources of melatonin. The gut microbiota helps produce melatonin from tryptophan, and melatonin has been shown to have a beneficial effect on gut barrier function and microbial population. Dysbiosis of the intestinal microbiota is associated with bacterial imbalance and decreased beneficial microbial metabolites, including melatonin. In this way, low melatonin levels may be related to several human diseases. Melatonin has shown both preventive and therapeutic effects against various conditions, including neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review was aimed to discuss the role of melatonin in the body, and to describe the possible relationship between gut microbiota and melatonin production, as well as the potential therapeutic effects of melatonin on neurological diseases.

Analyzing the expression pattern of the noncoding RNAs (HOTAIR, PVT-1, XIST, H19, and miRNA-34a) in PBMC samples of patients with COVID-19, according to the disease severity in Iran during 2022-2023: A cross-sectional study.

Background and aims: MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are well-known types of noncoding RNAs (ncRNAs), which have been known as the key regulators of gene expression. They can play critical roles in viral infection by regulating the host immune response and interacting with genes in the viral genome. In this regard, ncRNAs can be employed as biomarkers for viral diseases. The current study aimed to evaluate peripheral blood mononuclear cell (PBMC) ncRNAs (lncRNAs-homeobox C antisense intergenic RNA [HOTAIR], -H19, X-inactive-specific transcript [XIST], plasmacytoma variant translocation 1 [PVT-1], and miR-34a) as diagnostic biomarkers to differentiate severe COVID-19 cases from mild ones. Methods: Candidate ncRNAs were selected according to previous studies and assessed by real-time polymerase chain reaction in the PBMC samples of patients with severe coronavirus disease 2019 (COVID-19) (n = 40), healthy subjects (n = 40), and mild COVID-19 cases (n = 40). Furthermore, the diagnostic value of the selected ncRNAs was assessed by analyzing the receiver-operating characteristic (ROC). Results: The results demonstrated that the expression pattern of the selected ncRNAs was significantly different between the studied groups. The levels of HOTAIR, XIST, and miR-34a were remarkably overexpressed in the severe COVID-19 group in comparison with the mild COVID-19 group, and in return, the PVT-1 levels were lower than in the mild COVID-19 group. Interestingly, the XIST expression level in men with severe COVID-19 was higher compared to women with mild COVID-19. ROC results suggested that HOTAIR and PVT-1 could serve as useful biomarkers for screening mild COVID-19 from severe COVID-19. Conclusions: Overall, different expression patterns of the selected ncRNAs and ROC curve results revealed that these factors can contribute to COVID-19 pathogenicity and can be considered diagnostic markers of COVID-19 severe outcomes.

Oncoviruses: Induction of cancer development and metastasis by increasing anoikis resistance.

The phenomenon of cell death is a vital aspect in the regulation of aberrant cells such as cancer cells. Anoikis is a kind of cell death that occurs when cells get separated from the extracellular matrix. Some cancer cells can inhibit anoikis in order to progress metastasis. One of the key variables that might be implicated in anoikis resistance (AR) is viral infections. The most important viruses involved in this process are Epstein-Barr virus, human papillomavirus, hepatitis B virus, human herpes virus 8, human T-cell lymphotropic virus type 1, and hepatitis C virus. A better understanding of how carcinogenic viruses suppress anoikis might be helpful in developing an effective treatment for virus-associated cancers. In the current study, we review the role of the mentioned viruses and their gene products in anoikis inhibition.

Rare pyoderma gangrenosum correlated with systemic lupus erythematosus: A case report.

The simultaneous occurrence of pyoderma gangrenosum and systemic lupus erythematosus is exceedingly rare and poses diagnostic challenges due to the similarity of skin manifestations in both conditions. The exact relationship between the two conditions remains unclear; however, it is hypothesized that immune dysregulation and neutrophilic infiltration may play a role in the development of pyoderma gangrenosum in SLE patients. Clinicians should be vigilant in recognizing such uncommon associations to ensure prompt and appropriate management.

MiRNA-related metastasis in oral cancer: moving and shaking.

Across the world, oral cancer is a prevalent tumor. Over the years, both its mortality and incidence have grown. Oral cancer metastasis is a complex process involving cell invasion, migration, proliferation, and egress from cancer tissue either by lymphatic vessels or blood vessels. MicroRNAs (miRNAs) are essential short non-coding RNAs, which can act either as tumor suppressors or as oncogenes to control cancer development. Cancer metastasis is a multi-step process, in which miRNAs can inhibit or stimulate metastasis at all stages, including epithelial-mesenchymal transition, migration, invasion, and colonization, by targeting critical genes in these pathways. On the other hand, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two different types of non-coding RNAs, can regulate cancer metastasis by affecting gene expression through cross-talk with miRNAs. We reviewed the scientific literature (Google Scholar, Scopus, and PubMed) for the period 2000-2023 to find reports concerning miRNAs and lncRNA/circRNA-miRNA-mRNA networks, which control the spread of oral cancer cells by affecting invasion, migration, and metastasis. According to these reports, miRNAs are involved in the regulation of metastasis pathways either by directly or indirectly targeting genes associated with metastasis. Moreover, circRNAs and lncRNAs can induce or suppress oral cancer metastasis by acting as competing endogenous RNAs to inhibit the effect of miRNA suppression on specific mRNAs. Overall, non-coding RNAs (especially miRNAs) could help to create innovative therapeutic methods for the control of oral cancer metastases.

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug nirmatrelvir can keep SARS-CoV-2 from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV protease inhibitor, ritonavir, to create Paxlovid (Nirmatrelvir/Ritonavir). The metabolizing enzyme cytochrome P450 3 A is inhibited by ritonavir to lengthen the half-life of nirmatrelvir, so rintonavir acts as a pharmacological enhancer. Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome. Nevertheless, there are still several unanswered questions. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, and also their safety and possible side effects.

Evaluation of MicroRNA Expression Pattern (miR-28, miR-181a, miR-34a, and miR-31) in Patients with COVID-19 Admitted to ICU and Diabetic COVID-19 Patients.

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

Correlations between single nucleotide polymorphisms in obsessive-compulsive disorder with the clinical features or response to therapy.

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder, in which the patient endures intrusive thoughts or is compelled to perform repetitive or ritualized actions. Many cases of OCD are considered to be familial or heritable in nature. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of OCD. Among the internal factors, genetic modifications play a critical role in the pathophysiological process. Despite many investigations performed to determine the candidate genes, the precise genetic factors involved in the disease remain largely undetermined. The present review summarizes the single nucleotide polymorphisms that have been proposed to be associated with OCD symptoms, early onset disease, neuroimaging results, and response to therapy. This information could help us to draw connections between genetics and OCD symptoms, better characterize OCD in individual patients, understand OCD prognosis, and design more targeted personalized treatment approaches.

Non-Coding RNAs and Oral Cancer: Small Molecules With Big Functions.

Oral cancer remains a major public concern with considerable socioeconomic impact in the world. Despite substantial advancements have been made in treating oral cancer, the five-year survival rate for oral cancer remained undesirable, and the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Noncoding RNAs (ncRNAs) include transfer RNAs (tRNAs), as well as small RNAs such as microRNAs, and the long ncRNAs such as HOTAIR are a large segment of the transcriptome that do not have apparent protein-coding roles, but they have been verified to play important roles in diverse biological processes, including cancer cell development. Cell death, such as apoptosis, necrosis, and autophagy, plays a vital role in the progression of cancer. A better understanding of the regulatory relationships between ncRNAs and these various types of cancer cell death is therefore urgently required. The occurrence and development of oral cancer can be controlled by increasing or decreasing the expression of ncRNAs, a method which confers broad prospects for oral cancer treatment. Therefore, it is urgent for us to understand the influence of ncRNAs on the development of different modes of oral tumor death, and to evaluate whether ncRNAs have the potential to be used as biological targets for inducing cell death and recurrence of chemotherapy. The purpose of this review is to describe the impact of ncRNAs on cell apoptosis and autophagy in oral cancer in order to explore potential targets for oral cancer therapy.

Microfluidics for detection of exosomes and microRNAs in cancer: State of the art.

Exosomes are small extracellular vesicles with sizes ranging from 30-150 nanometers that contain proteins, lipids, mRNAs, microRNAs, and double-stranded DNA derived from the cells of origin. Exosomes can be taken up by target cells, acting as a means of cell-to-cell communication. The discovery of these vesicles in body fluids and their participation in cell communication has led to major breakthroughs in diagnosis, prognosis, and treatment of several conditions (e.g., cancer). However, conventional isolation and evaluation of exosomes and their microRNA content suffers from high cost, lengthy processes, difficult standardization, low purity, and poor yield. The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes involved in cancer. Microfluidics techniques hold promise for advances in development of diagnostic and prognostic devices. This review covers ongoing research on microfluidics devices for detection of microRNAs and exosomes as biomarkers and their translation to point-of-care and clinical applications.

The expression patterns of MALAT-1, NEAT-1, THRIL, and miR-155-5p in the acute to the post-acute phase of COVID-19 disease.

INTRODUCTION: One of the hallmarks of COVID-19 is overwhelming inflammation, which plays a very important role in the pathogenesis of COVID-19. Thus, identification of inflammatory factors that interact with the SARS-CoV-2 can be very important to control and diagnose the severity of COVID-19. The aim of this study was to investigate the expression patterns of inflammation-related non-coding RNAs (ncRNAs) including MALAT-1, NEAT-1, THRIL, and miR-155-5p from the acute phase to the recovery phase of COVID-19. METHODS: Total RNA was extracted from Peripheral Blood Mononuclear Cell (PBMC) samples of 20 patients with acute COVID-19 infection and 20 healthy individuals and the expression levels of MALAT-1, NEAT-1, THRIL, and miR-155-5p were evaluated by real-time PCR assay. Besides, in order to monitor the expression pattern of selected ncRNAs from the acute phase to the recovery phase of COVID-19 disease, the levels of ncRNAs were re-measured 6‒7 weeks after the acute phase. RESULT: The mean expression levels of MALAT-1, THRIL, and miR-155-5p were significantly increased in the acute phase of COVID-19 compared with a healthy control group. In addition, the expression levels of MALAT-1 and THRIL in the post-acute phase of COVID-19 were significantly lower than in the acute phase of COVID-19. According to the ROC curve analysis, these ncRNAs could be considered useful biomarkers for COVID-19 diagnosis and for discriminating between acute and post-acute phase of COVID-19. DISCUSSION: Inflammation-related ncRNAs (MALAT-1, THRIL, and miR-150-5p) can act as hopeful biomarkers for the monitoring and diagnosis of COVID-19 disease.

MicroRNA let-7 and viral infections: focus on mechanisms of action.

MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.

The expression patterns of MALAT-1, NEAT-1, THRIL, and miR-155-5p in the acute to the post-acute phase of COVID-19 disease

ABSTRACT Introduction: One of the hallmarks of COVID-19 is overwhelming inflammation, which plays a very important role in the pathogenesis of COVID-19. Thus, identification of inflammatory factors that interact with the SARS-CoV-2 can be very important to control and diagnose the severity of COVID-19. The aim of this study was to investigate the expression patterns of inflammation-related non-coding RNAs (ncRNAs) including MALAT-1, NEAT-1, THRIL, and miR-155-5p from the acute phase to the recovery phase of COVID-19. Methods: Total RNA was extracted from Peripheral Blood Mononuclear Cell (PBMC) samples of 20 patients with acute COVID-19 infection and 20 healthy individuals and the expression levels of MALAT-1, NEAT-1, THRIL, and miR-155-5p were evaluated by real-time PCR assay. Besides, in order to monitor the expression pattern of selected ncRNAs from the acute phase to the recovery phase of COVID-19 disease, the levels of ncRNAs were re-measured 6-7 weeks after the acute phase. Result: The mean expression levels of MALAT-1, THRIL, and miR-155-5p were significantly increased in the acute phase of COVID-19 compared with a healthy control group. In addition, the expression levels of MALAT-1 and THRIL in the post-acute phase of COVID-19 were significantly lower than in the acute phase of COVID-19. According to the ROC curve analysis, these ncRNAs could be considered useful biomarkers for COVID-19 diagnosis and for discriminating between acute and post-acute phase of COVID-19. Discussion: Inflammation-related ncRNAs (MALAT-1, THRIL, and miR-150-5p) can act as hopeful biomarkers for the monitoring and diagnosis of COVID-19 disease.

Oncogenic viruses and chemoresistance: What do we know?

Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.

Joint application of biochemical markers and imaging techniques in the accurate and early detection of glioblastoma.

Glioblastoma is a primary brain tumor with the most metastatic effect in adults. Despite the wide range of multidimensional treatments, tumor heterogeneity is one of the main causes of tumor spread and gives great complexity to diagnostic and therapeutic methods. Therefore, featuring noble noninvasive prognostic methods that are focused on glioblastoma heterogeneity is perceived as an urgent need. Imaging neuro-oncological biomarkers including MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation status, tumor grade along with other tumor characteristics and demographic features (e.g., age) are commonly referred to during diagnostic, therapeutic and prognostic processes. Therefore, the use of new noninvasive prognostic methods focused on glioblastoma heterogeneity is considered an urgent need. Some neuronal biomarkers, including the promoter methylation status of the promoter MGMT, the characteristics and grade of the tumor, along with the patient's demographics (such as age and sex) are involved in diagnosis, treatment, and prognosis. Among the wide array of imaging techniques, magnetic resonance imaging combined with the more physiologically detailed technique of H-magnetic resonance spectroscopy can be useful in diagnosing neurological cancer patients. In addition, intracranial tumor qualitative analysis and sometimes tumor biopsies help in accurate diagnosis. This review summarizes the evidence for biochemical biomarkers being a reliable biomarker in the early detection and disease management in GBM. Moreover, we highlight the correlation between Imaging techniques and biochemical biomarkers and ask whether they can be combined.

Non-Coding RNAs and Brain Tumors: Insights Into Their Roles in Apoptosis.

A major terrifying ailment afflicting the humans throughout the world is brain tumor, which causes a lot of mortality among pediatric and adult solid tumors. Several major barriers to the treatment and diagnosis of the brain tumors are the specific micro-environmental and cell-intrinsic features of neural tissues. Absence of the nutrients and hypoxia trigger the cells' mortality in the core of the tumors of humans' brains: however, type of the cells' mortality, including apoptosis or necrosis, has been not found obviously. Current studies have emphasized the non-coding RNAs (ncRNAs) since their crucial impacts on carcinogenesis have been discovered. Several investigations suggest the essential contribution of such molecules in the development of brain tumors and the respective roles in apoptosis. Herein, we summarize the apoptosis-related non-coding RNAs in brain tumors.

Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis.

BACKGROUND: The aim of this study is to address the role of HPV in prostate cancer (PCa) development through the inducement of resistance to anoikis. METHODS: In this case-control study, prostate tissues and blood samples were collected from 116 individuals, including 72 cases with PCa and 44 non-malignant prostate tissue samples as a control group. The expression level of HPV genes (E2, E6, and E7) and cellular genes including anti-apoptotic mediators (Bcl-2 and survivin), tumor suppressor proteins (Rb and p53), and some mediators involved in anoikis resistance and invasiveness (E-cadherin, N-cadherin, Twist, PTPN13 and SLUG) were evaluated. RESULTS: HPV genome was identified in 36.1% cases and 15.9% control samples, additionally there was found to be a statistic significant association between the presence of HPV and PCa (OR = 1.64, 95% C.I = 0.8-1.8, P-value = 0.023). HPV genotype 16 and 18 were the most prevalent genotype in both in the PCa group and the control group. The expression level of the tumor suppressor proteins (Rb and p53) and anti-apoptotic mediators (Bcl-2 and Survivin) were significantly decreased and increased, respectively, in the HPV-positive specimens compared to the HPV-negative specimens. Furthermore, the mean expression level of N-cadherin, SLUG, and TWIST in the HPV-positive specimens was higher than HPV-negative specimens while the mean expression level of PTPN-13 and E-cadherin genes in the HPV-positive specimens was lower than HPV-negative specimens. CONCLUSION: Our study suggests that HPV infection may be involved in the development of PCa metastases by modulating anoikis resistance related genes.

The role of miR-146a in viral infection.

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.