Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.

Exosomes derived from mesenchymal stem cells: A promising cell-free therapeutic tool for cutaneous wound healing.

Skin wound healing is a multifaceted process involving a cascade of molecular and cellular procedures that occur in four different phases: (a) hemostasis, (b) inflammation, (c) proliferation, and (d) tissue remodeling. Prolonged wound healing in skin is still a major challenge in treatment of wounds. Mesenchymal stem cells (MSCs) accelerate cutaneous wound healing through their paracrine activity. Exosomes are one of the key secretory products of MSCs, mimicking the effects of parental MSCs in skin wound healing process. Exosomes are small membrane vesicles (30-150 nm in diameter) that originate from endosomal pathways and transport numerous biomolecules, including DNAs, messenger RNAs, microRNAs, lipids, and proteins. They can be taken up by target cells and release their contents to modulate the activity of recipient cells. Exosomes derived from mesenchymal stem cells (MSC-Exo) reduce inflammation, promote proliferation, inhibit apoptosis, and enhance angiogenesis in skin wound healing process. Therefore, exosomes are emerging as novel cell-cell communication mediators and have opened a novel viewpoint for developing cell-free therapies. This review aims to demonstrate the roles of exosomes in each step of skin wound healing through a comprehensive literature search.

Partial sequence conservation of SARS-CoV-2 NSP-2, NSP-12, and Spike in stool samples from Abadan, Iran.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the clinical manifestations of the virus have undergone many changes. Recently, there have been many reports on gastrointestinal symptoms in COVID-19 patients. This study is aimed to perform a detailed phylogenetic study and assessment of different SNVs in the RNA genome of viruses isolated from fecal samples of patients with COVID-19 who have gastrointestinal symptoms, which can help better understand viral pathogenesis. In the present study, 20 fecal samples were collected by written consent from COVID-19 patients. According to the manufacturer's protocol, virus nucleic acid was extracted from stool samples and the SARS-CoV-2 genome presence in stool samples was confirmed by RT-PCR assay. Three viral genes, S, nsp12, and nsp2, were amplified using the reverse transcription polymerase chain reaction (RT-PCR) method and specific primers. Multiple sequencing alignment (MSA) was performed in the CLC word bench, and a phylogenetic tree was generated by MEGA X based on the neighbor-joining method. Of all cases, 11 (55%) were males. The mean age of the patients was 33.6 years. Diabetes (70%) and blood pressure (55%) were the most prevalent comorbidities. All 20 patients were positive for SARS-CoV-2 infection in respiratory samples. Molecular analysis investigation among 20 stool samples revealed that the SARS-CoV-2 genome was found among 10 stool samples; only three samples were used for sequencing. The polymorphism and phylogenetic analysis in SARS-CoV-2 showed great similarity among all of the evaluated genes with the Wuhan reference sequence and all of the current variants of concern (VOCs). The current study represents a great similarity in polymorphism and phylogenetic analysis of the SARS-CoV-2 isolates with the Wuhan reference sequence and all of the current VOC in the particular evaluated partial sequences of S, nsp12, and nsp2.

xsGastrointestinal symptoms are associated with a lower risk of hospitalization and mortality and Outcomes in COVID-19.

BACKGROUND: We aimed to find the association between gastrointestinal (GI) and respiratory symptoms with mortality and hospitalization among COVID-19 patients. METHODS: We analyzed the registered data of COVID-19 patients from February 20, 2020, to March 10, 2021. Depending on the patients' disease symptoms, four categories were defined: patients with only GI symptoms, patients with only respiratory symptoms, patients with both symptoms, and patients with other symptoms. Logistic regression analysis was used to assess the association of groups with outcomes. RESULTS: A total of 42,964 patients from 23 hospitals were included, of which 26.5% patients had at least one or more GI symptoms. Of total patients, 51.58% patients were hospitalized among which 22.8% had at least one or more GI symptoms. GI symptoms significantly decreased the odds of mortality (OR 0.72, 95% CI 0.56-0.92), but respiratory symptoms increased the odds for mortality (1.36: 1.24-1.50), compared with patients with other symptoms. Moreover, the odds ratio of patients who had both respiratory and GI symptoms increased (1.52: 1.31-1.78) compared with patients with other symptoms. The same results were observed for hospitalization as the outcome. CONCLUSIONS: Our study showed that the presence of GI symptoms in COVID-19 at the time of admission was associated with a lower odds of hospitalization and mortality; however, this association had higher odds for respiratory symptoms.

Clinical Symptoms and Types of Samples Are Critical Factors for the Molecular Diagnosis of Symptomatic COVID-19 Patients: A Systematic Literature Review.

BACKGROUND: Currently, a novel coronavirus found in 2019 known as SARS-CoV-2 is the etiological agent of the COVID-19 pandemic. Various parameters including clinical manifestations and molecular evaluation can affect the accuracy of diagnosis. This review aims to discuss the various clinical symptoms and molecular evaluation results in COVID-19 patients, to point out the importance of onset symptoms, type, and timing of the sampling, besides the methods that are used for detection of SARS-CoV-2. METHODS: A systematic literature review of current articles in the Web of Science, PubMed, Scopus, and EMBASE was conducted according to the PRISMA guideline. RESULTS: Of the 12946 patients evaluated in this investigation, 7643 were confirmed to be COVID-19 positive by molecular techniques, particularly the RT-PCR/qPCR combined technique (qRT-PCR). In most of the studies, all of the enrolled cases had 100% positive results for molecular evaluation. Among the COVID-19 patients who were identified as such by positive PCR results, most of them showed fever or cough as the primary clinical signs. Less common symptoms observed in clinically confirmed cases were hemoptysis, bloody sputum, mental disorders, and nasal congestion. The most common clinical samples for PCR-confirmed COVID-19 patients were obtained from throat, oropharyngeal, and nasopharyngeal swabs, while tears and conjunctival secretions seem to be the least common clinical samples for COVID-19 diagnosis among studies. Also, different conserved SARS-CoV-2 gene sequences could be targeted for qRT-PCR detection. The suggested molecular assay being used by most laboratories for the detection of SARS-CoV-2 is qRT-PCR. CONCLUSION: There is a worldwide concern on the COVID-19 pandemic and a lack of well-managed global control. Hence, it is crucial to update the molecular diagnostics protocols for handling the situation. This is possible by understanding the available advances in assays for the detection of the SARS-CoV-2 infection. Good sampling procedure and using samples with enough viral loads, also considering the onset symptoms, may reduce the qRT-PCR false-negative results in symptomatic COVID-19 patients. Selection of the most efficient primer-probe for target genes and samples containing enough viral loads to search for the existence of SARS-CoV-2 helps detecting the virus on time using qRT-PCR.

HPV infections in retinoblastoma: a systematic review.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma. METHODS: For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening. RESULTS: Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks. CONCLUSION: The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.

The Role of Bacterial and Fungal Human Respiratory Microbiota in COVID-19 Patients.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic with millions of infected patients. Alteration in humans' microbiota was also reported in COVID-19 patients. The alteration in human microbiota may contribute to bacterial or viral infections and affect the immune system. Moreover, human's microbiota can be altered due to SARS-CoV-2 infection, and these microbiota changes can indicate the progression of COVID-19. While current studies focus on the gut microbiota, it seems necessary to pay attention to the lung microbiota in COVID-19. This study is aimed at reviewing respiratory microbiota dysbiosis among COVID-19 patients to encourage further studies on the field for assessment of SARS-CoV-2 and respiratory microbiota interaction.

COVID-19 associated central nervous system manifestations, mental and neurological symptoms: a systematic review and meta-analysis.

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral infections can infect the nervous system; these viral infections can present a wide range of manifestation. The aim of the current study was to systematically review the COVID-19 associated central nervous system manifestations, mental and neurological symptoms. For that we conducted a comprehensive systematic literature review of four online databases, including Web of Science, PubMed, Scopus and Embase. All relevant articles that reported psychiatric/psychological symptoms or disorders in COVID-19 without considering time and language restrictions were assessed. All the study procedures were performed based on the PRISMA criteria. Due to the screening, 14 studies were included. The current study result indicated that, the pooled prevalence of CNS or mental associated disorders with 95% CI was 50.68% (6.68-93.88). The most prevalence symptoms were hyposmia/anosmia/olfactory dysfunction (number of study: 10) with 36.20% (14.99-60.51). Only one study reported numbness/paresthesia and dysphonia. Pooled prevalence of numbness/paresthesia and dysphonia was 5.83% (2.17-12.25) and 2.39% (10.75-14.22). The pooled prevalence of depression and anxiety was 3.52% (2.62-4.54) and 13.92% (9.44-19.08). Our findings demonstrate that COVID-19 has a certain relation with neurological symptoms. The hypsomia, anosmia or olfactory dysfunction was most frequent symptom. Other symptoms were headache or dizziness, dysgeusia or ageusia, dysphonia and fatigue. Depression, anxiety, and confusion were less frequent symptoms.

A review on EBV encoded and EBV-induced host microRNAs expression profile in different lymphoma types.

Previous literature supports the variations in microRNAs expression levels among lymphoma patients due to EBV infection. These alterations can be observed in both EBV-encoded-microRNAs and EBV-induced cellular microRNAs. Moreover, changes in the microRNA profile could be significant in disease progression. This study aimed to assess published literature to obtain a microRNA profile for both EBV-encoded microRNAs and EBV-induced cellular microRNAs among lymphoma patients. We searched common available electronic databases by using relevant keywords. The result demonstrated that EBV infection could alter the microRNA expression levels among lymphoma patients. In Burkitt lymphoma, hsa-miR197 and miR510 were most frequently assessed human micro RNAs. Also, miR-BART6-3P and miR-BART17-5P were the most frequent viral micro RNAs in Burkitt lymphoma. Other human important micro RNAs were hsa-miR155 (in Diffuse large B cell lymphoma (DLBCL)), hsa-miR145 (in Nasal natural killer T cell lymphoma (NNKTCL)), miR-96, miR-128a, miR-128b, miR-129, and miR-205 (in Classic Hodgkin lymphoma (CHL)), miR-21, miR-142-3P, miR-126, miR-451 and miR-494-3P (in Nasal natural killer cell lymphoma (NNKCL)). Also, viral assessed micro RNAs were miR-BART1-5P (in DLBCL and NNKTCL), miR-BART-5 (in CHL), and EBV-miR-BART20-5P (in NNKCL). In conclusion, it could be suggested that EBV-encoded-microRNAs and EBV-induced cellular-microRNAs can be utilized as helpful factors for different types of lymphoma diagnoses or prognostic factors. Moreover, the mentioned microRNAs can also be promising therapeutic targets and can be used to modulate the oncogenes.

A literature review on the parvovirus B19 infection in sickle cell anemia and ß-thalassemia patients.

BACKGROUND: Parvovirus B19 is the causative agent for erythema infectiosum, and also as a potentially life-threatening infectious agent, it is mainly presented in high erythrocyte turnover patients. Sickle cell disease (SCD) is an inherited monogenic hematological disorder resulting from the mutations in the hemoglobin ß-chain gene. Thalassemia is a hereditary hematological syndrome that happens in consequence of deficiencies in the production of one or more globin chains. We summarize current knowledge about the prevalence rates of the parvovirus B19 infection in sickle cell anemia and thalassemia patients. METHODS: Several online databases were searched including, Scopus, EMBASE, Web of Science, Google Scholar, and PubMed, which were performed amidst 2009-2019 by using distinct keywords: "Thalassemia," "Parvovirus," "Anemia," "Sickle cell anemia," "parvoviridae," "parvoviridae infection," and "parvovirus B19." RESULTS: Search results indicated 4 and 7 studies for the prevalence of the parvovirus B19 in ß-thalassemia and SCD, respectively. Among the ß-thalassemia patients, the B19V seroprevalence for IgG and IgM were ranged from 18.2-81% and 14.5-41.1%, respectively; meanwhile, B19V DNA positively results was 4-15.3%. Moreover, in the SCD group, the extent of B19V IgG was varied from 37.6 to 65.9% and that of IgM was in a range of 2.9-30%, and the DNA detection rate was 4-54%. CONCLUSION: B19V seroprevalence changes in several conditions including, different epidemiological features, socio-economic status, and overpopulation. Age can expand the incidence of anti-B19V IgG/IgM in SCD and beta-thalassemia patients. Reinfection and diverse genotypes are relevant factors in the seroprevalence of B19v. The patients' immunological-hematological station and higher abundance of transfusions can affect the B19V seroprevalence in SCD and beta-thalassemia group. Further investigations in this field could be suggested to better understand the virus distribution in this susceptible population of patients.