The relationship between autophagy and respiratory viruses.

Respiratory viruses have caused severe global health problems and posed essential challenges to the medical community. In recent years, the role of autophagy as a critical process in cells in viral respiratory diseases has been noticed. One of the vital catabolic biological processes in the body is autophagy. Autophagy contributes to energy recovery by targeting and selectively directing foreign microorganisms, organelles, and senescent intracellular proteins to the lysosome for degradation and phagocytosis. Activation or suppression of autophagy is often initiated when foreign pathogenic organisms such as viruses infect cells. Because of its antiviral properties, several viruses may escape or resist this process by encoding viral proteins. Viruses can also use autophagy to enhance their replication or prolong the persistence of latent infections. Here, we provide an overview of autophagy and respiratory viruses such as coronavirus, rhinovirus, parainfluenza, influenza, adenovirus, and respiratory syncytial virus, and examine the interactions between them and the role of autophagy in the virus-host interaction process and the resulting virus replication strategy.

Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

BACKGROUND: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. METHODS AND RESULTS: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). CONCLUSIONS: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia.

The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies. Video Abstract.

The mysterious anelloviruses: investigating its role in human diseases.

Anelloviruses (AVs) that infect the human population are members of the Anelloviridae family. They are widely distributed in human populations worldwide. Torque teno virus (TTV) was the first virus of this family to be identified and is estimated to be found in the serum of 80-90% of the human population. Sometime after the identification of TTV, Torque teno mini virus (TTMV) and Torque teno midi virus (TTMDV) were also identified and classified in this family. Since identifying these viruses, have been detected in various types of biological fluids of the human body, including blood and urine, as well as vital organs such as the liver and kidney. They can be transmitted from person to person through blood transfusions, fecal-oral contact, and possibly sexual intercourse. Recent studies on these newly introduced viruses show that although they are not directly related to human disease, they may be indirectly involved in initiating or exacerbating some human population-related diseases and viral infections. Among these diseases, we can mention various types of cancers, immune system diseases, viral infections, hepatitis, and AIDS. Also, they likely use the microRNAs (miRNAs) they encode to fulfill this cooperative role. Also, in recent years, the role of proliferation and their viral load, especially TTV, has been highlighted to indicate the immune system status of immunocompromised people or people who undergo organ transplants. Here, we review the possible role of these viruses in diseases that target humans and highlight them as important viruses that require further study. This review can provide new insights to researchers.

Mature cystic ovarian teratoma with squamous cell carcinoma transformation: a case report and literature review.

OBJECTIVES: Cancerous transformation in mature cystic ovarian teratoma is rare. Herein, we reported a case of squamous cell carcinoma transformation in mature cystic ovarian teratoma and performed an in-depth literature review to highlight the risk factors, prognosis, and suggested treatment for these patients. CASE PRESENTATION: We report a 66-years old postmenopausal woman diagnosed with a 120×90 (mm) mass at the left adnexa compatible with mature cystic ovarian teratoma. Following resection, the histopathological investigations showed malignant transformation in her mature cystic ovarian teratoma, and the immunohistochemistry for cytokeratin (CK) 5/6 and tumor protein 63 (P63) indicated squamous cell carcinoma transformation. She has been observed for her stage IA tumor and has been cancer-free for 6 months. CONCLUSIONS: Although malignant transformation in mature cystic ovarian teratoma is rare, it should be suspected if certain risk factors, e.g., elderly and high tumor size, exist. Stage IA patients' prognosis is favorable, and chemotherapy is not recommended.

Exosome-mediated regulation of inflammatory pathway during respiratory viral disease.

Viruses have developed many mechanisms by which they can stimulate or inhibit inflammation and cause various diseases, including viral respiratory diseases that kill many people every year. One of the mechanisms that viruses use to induce or inhibit inflammation is exosomes. Exosomes are small membrane nanovesicles (30-150 nm) released from cells that contain proteins, DNA, and coding and non-coding RNA species. They are a group of extracellular vesicles that cells can take up to produce and mediate communication. Intercellular effect exosomes can deliver a broad confine of biological molecules, containing nucleic acids, proteins, and lipids, to the target cell, where they can convey therapeutic or pathogenic consequences through the modulation of inflammation and immune processes. Recent research has shown that exosomes can deliver entire virus genomes or virions to distant target cells, then the delivered viruses can escape the immune system and infect cells. Adenoviruses, orthomyxoviruses, paramyxoviruses, respiratory syncytial viruses, picornaviruses, coronaviruses, and rhinoviruses are mostly related to respiratory diseases. In this article, we will first discuss the current knowledge of exosomes. We will learn about the relationship between exosomes and viral infections, and We mention the inflammations caused by viruses in the airways, the role of exosomes in them, and finally, we examine the relationship between the viruses as mentioned earlier, and the regulation of inflammatory pathways that play a role in causing the disease.

T Lymphocyte Characteristic Changes Under Serum Cytokine Deviations and Prognostic Factors of COVID-19 in Pregnant Women.

Physiological changes during pregnancy make the individuals more susceptible to severe respiratory diseases. Hence, pregnant women with coronavirus disease 2019 (COVID-19) are likely at a higher risk. We investigated the effects of COVID-19 on T cell response and serum cytokine profile in pregnant patients. Peripheral blood mononuclear cells (PBMCs) of women with COVID-19 were collected during the first trimester of pregnancy, and the percentage of total lymphocytes, as well as CD4 + and CD8 + T cells, was assessed using flow cytometry. The expression of the programmed death-1 (PD-1) marker for exhausted T cells was evaluated. Additionally, the serum samples were provided to evaluate the levels of antiviral and proinflammatory cytokines, as well as laboratory serological tests. Pregnant women with COVID-19 presented lymphopenia with diminished CD4 + and CD8 + T cells. Besides, high expression levels of the PD-1 gene and protein were observed on PBMCs and T cells, respectively, when compared with normal pregnant individuals. Moreover, serum levels of TNF-α, IL-6, IL-1ß, and IL-2 receptor were notably enhanced, while IFN-I α/ß values were significantly decreased in the patients when compared with controls. Furthermore, hyperlipidemia, hyperglycemia, and hypertension were directly correlated with the disease although serum albumin and vitamin D3 levels adversely affected the viral infection. Our study showed extreme lymphopenia and poor T cell response while elevated values of serum inflammatory cytokines in infected pregnant women. Moreover, a hypertension background or metabolic changes, including hyperlipidemia, hyperglycemia, and vitamin D3 or albumin deficiency, might be promising prognostic factors in pregnant women with COVID-19.

The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL).

In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.

Global haplotype distribution of Babesia ovis inferred by 18S rRNA sequences; a phylogeographical systematic review.

The genetic variability of apicomplexan parasite Babesia species is a principal strategy used by piroplasma to evade their hosts' immune responses. The purpose of this review was to evaluate our current knowledge on global haplotype distribution and phylogeography of Babesia ovis derived from sheep, goat, horse and ixodid (hard) ticks. Bibliographic English databases were searched from 2017 to 2023, identifying a total of 11 publications. The 18S ribosomal RNA (18S rRNA) sequences of B. ovis from Asia, Europe, and Africa were retrieved and subjected to estimate the genetic diversity and phylogenetic assessment. A haplotype network indicated a total of 29 haplotypes being classified into two distinct geographical haplogroups I and II including Nigeria and Uganda-derived B. ovis isolates. A moderately high level of genetic diversity was characterized in sheep/tick-derived B. ovis isolates originating from Iraq (Haplotype diversity: 0.781) and Turkey (Hd: 0.841). Based on the cladistic phylogenetic tree, two geographically different lineages of A and B were genetically differentiated except for Turkish isolates, indicating haplotype migration occurred between various geographical clades. In addition, the topology of UPGMA tree indicated that B. ovis population has a distinct clade compared to the rest clades of ovine babesiosis (B. crassa and B. motasi). The present results strengthen our knowledge to evaluate the evolutionary paradigms and transmission dynamics of B. ovis in different regions of the world; also it will provide groundwork for public health policy to control ovine babesiosis.

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.

Activated carbon/metal-organic framework nanocomposite: Preparation and photocatalytic dye degradation mathematical modeling from wastewater by least squares support vector machine.

Herein, Kiwi peel activated carbon (AC), Materials Institute Lavoisier (MIL-88B (Fe), and AC/MIL-88B (Fe) composite were synthesized and used as catalysts to degrade Reactive Red 198. The material properties were analyzed by the FTIR, BET-BJH, XRD, FESEM, EDX, TGA, and UV-Vis/DRS. The BET surface area of AC, MIL-88B (Fe) and AC/MIL-88B (Fe) was 1113.3, 150.7, and 199.4 m2/g, respectively. The band gap values (Eg) estimated by Tauc plot method, were obtained 5.06, 4.19 and 3.79 eV for AC, MIL-88B (Fe) and AC/MIL-88B (Fe), respectively. The results indicated that the AC/MIL-88B (Fe) composite had higher photocatalytic activity (99%) than that of pure AC (79%) and MIL-88B (Fe) catalysts (87%). The decolorization kinetic was matched well with the second-order model. Moreover, the data were modeled using least squares support vector machine which optimized with Cuckoo optimization algorithm. The optimal parameters were found 0.837 and 3.49e+02 based on σ2 and γ values, respectively. The mean square error (MSE) and correlation coefficient (R2) values were obtained 3.97 and 0.948. Therefore, the attained data, materials characterization and prediction of modeling validate the composite form of MIL-88B(Fe) with new AC, had better photocatalytic activity in comparison with the individual form.

Why People Choose to Volunteer? Women Health Volunteers' Activities, Reasons for Joining and Leaving.

Introduction: Women health volunteers are the link between people and healthcare workers. They play an important role in health education activities, following up families under coverage, and updating the demographic data to health centers. This study was performed to uncover women health volunteers' activities, reasons for joining and leaving from the program. Methods: A qualitative study design was used to conduct the study. Through purposive sampling technique, twenty -four in-depth semi-structured individual interviews and two focused group discussions with women health volunteers and their supervisors were conducted in Tabriz, Iran. Data analysis implemented thematic analysis, using MAXQDA10. Results: The findings were generally categorized into three major themes, participation in promoting health, perceived benefit, and perceptual- environmental inhibitors. Participation in promoting health consisted of the sub-themes participation in educational programs, participation in health care. The sub-themes of perceived benefit included benefits from health care services and interest in having an active role in the community. The theme perceptual- environmental inhibitors involved the subthemes participation barriers and lack of innovation and inconsistency with social changes. Conclusion: Culture-building about the role of health volunteers, the valuing on their activities in the community, and informing program supervisors about the health volunteer's duties would help to retain health volunteers and also sustain their activities at the community level.

Cytotoxic and apoptosis inducing effect of some pyrano [3, 2-c] pyridine derivatives against MCF-7 breast cancer cells.

Anti-cancer activities of some pyrano-pyridines have been previously reported. Herein, we investigated anti-proliferative and apoptotic effects of the novel pyrano [3, 2-c] pyridine (P.P, TPM.P, 4-CP.P and 3-NP.P) compounds against MCF-7 breast cancer cells. The MCF-7 cells were cultured in the presence of various concentrations (20-200 µM) of the tested compounds for 3 days and the cell viability was determined by MTT assay. Induction of apoptosis was qualitatively assayed by acridine orange/ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, as well as quantitatively by Annexin V/PI double staining and cell cycle analysis. These compounds inhibited growth and proliferation of the MCF-7 cells in a dose- and time-dependent manner. The IC50 values of P.P, TPM.P, 4-CP.P and 3-NP.P after 24 h of exposure were calculated to be 100±5.0, 180±6.0, 60±4.0 and 140±5.0 µM, respectively. 4-CP.P was determined as the most potent compound and was chosen for further studies. The result of flow cytometric cell cycle analysis indicated an increase in sub-G1 population after 72 h treatment of the cells. Furthermore, this was accompanied by exposure of phosphatidylserine (PS) in the outer cell membrane after time course of treatment with the 4-CP.P. Based on these observations, the pyrano [3, 2-c] pyridines can be regarded as a valuable candidate for further pharmaceutical evaluations.

Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

BACKGROUND: Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. MATERIALS AND METHODS: Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. RESULTS: There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. CONCLUSION: Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

Breast and cervical cancer-screening uptake among females in Ardabil, northwest Iran: a community-based study.

PURPOSE: Breast and cervical cancers are the most commonly diagnosed type of cancer and cause of cancer-related deaths in Iranian females. In contrast to previous studies, this study was carried out with a large sample size for assessment of breast self-examination (BSE)-, clinical breast examination (CBE)-, mammography-, and Pap smear-uptake rates and determination of associations among these screening behaviors with sociodemographic and cognitive variables in Azeri females. MATERIALS AND METHODS: This was a cross-sectional, community-based study that was carried out among 1,134 females 20-60 years old during March-June 2016. Data-collection variables included sociodemographic questions, screening behaviors for breast and cervical cancer, self-efficacy, beliefs, and barriers to breast and cervical cancer screening. Collected data were analyzed by SPSS version 13 using χ2, Mann-Whitney U, and logistic regression tests. RESULTS: Among the 1,134 participants, 53.9%, 9.8%, and 28.1% had done BSE, CBE, and Pap smear tests, respectively, and among the 625 females aged >40 years, 187 (29.9%) had done the mammography test. Moreover, 416 (36.7%), 103 (16.5%), and 64 (5.6%) females had done BSE, mammography, and CBE regularly, respectively. Beliefs, barriers, income, health insurance, number of children, and age were all important factors for BSE and regular BSE and mammography. Females who had high belief scores were more likely to undertake mammography (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.03-1.5), regular mammography (OR: 4.2, 95% CI: 1.9-9.3), regular CBE (OR: 1.25, 95% CI: 1.2-1.3), and Pap smears (OR: 1.2, 95% CI: 1.1-1.4). Also, females who had high self-efficacy scores were more likely to perform regular BSE (OR: 1.8, 95% CI: 1.4-2.5) and mammography (OR: 2.5, 95% CI: 1.4-4.6) than females with lower self-efficacy scores. CONCLUSION: The frequency of breast and cervical cancer screening was low in our study. The findings of this study indicated that beliefs, self-efficacy, and barriers were important predictive factors of cancer-screening behavior among the females studied.

The Comparison of Dietary Behaviors among Rural Controlled and Uncontrolled Hypertensive Patients.

Nutrition is a dominant peripheral factor in increasing blood pressure; however, little information is available about the nutritional status of hypertensive patients in Iran. This study aimed to compare nutritional behaviors of the rural controlled and uncontrolled hypertensive patients and to determine the predictive power of nutritional behaviors from blood pressure. This cross-sectional study was conducted on 671 rural hypertensive patients, using multistage random sampling method in Ardabil city in 2013. Data were collected by a 3-day food record questionnaire. Nutritional data were extracted by Nutritionist 4 software and analyzed by the SPSS 18 software using Pearson correlation, multiple linear regression, ANOVA, and independent t-test. A significant difference was observed in the means of fat intake, cholesterol, saturated fat, sodium, energy, calcium, vitamin C, fiber, and nutritional knowledge between controlled and uncontrolled groups. In the controlled group, sodium, saturated fats, vitamin C, calcium, and energy intake explained 30.6% of the variations in blood pressure and, in the uncontrolled group, sodium, carbohydrate, fiber intake, and nutritional knowledge explained 83% of the variations in blood pressure. There was a significant difference in the nutritional behavior between the two groups and changes in blood pressure could be explained significantly by nutritional behaviors.