Enhanced Induction of Apoptosis and Cell Cycle Arrest in MCF-7 Breast Cancer and HT-29 Colon Cancer Cell Lines via Low-Dose Biosynthesis of Selenium Nanoparticles Utilizing Lactobacillus casei.

As a leading global cause of mortality, cancer continues to pose a significant challenge. The shortcomings of prevalent cancer treatments, such as surgery, radiation therapy, and chemotherapy, necessitate the exploration of alternative therapeutic strategies. Selenium nanoparticles (SeNPs) have emerged as a promising solution, with their synthesis being widely researched due to their potential applications. Among the diverse synthesis methods for SeNPs, the green chemistry approach holds a distinctive position within nanotechnology. This research delves into the anti-proliferative and anticancer properties of green-synthesized SeNPs via the cell-free supernatant (CFS) of Lactobacillus casei (LC-SeNPs), with a specific focus on MCF-7 and HT-29 cancer cell lines. SeNPs were synthesized employing the supernatant of L. casei. The characterization of these green-synthesized SeNPs was performed using TEM, FE-SEM, XRD, FT-IR, UV-vis, energy-dispersive X-ray spectroscopy, and DLS. The biological impact of LC-SNPs on MCF-7 and HT-29 cancer cells was examined via MTT, flow cytometry, scratch tests, and qRT-PCR. Both FE-SEM and TEM images substantiated the spherical shape of the synthesized nanoparticles. The biosynthesized LC-SNPs reduced the survival of MCF-7 (by 20%) and HT-29 (by 30%) cells at a concentration of 100 µg/mL. Flow cytometry revealed that LC-SNPs were capable of inducing 28% and 23% apoptosis in MCF-7 and HT-29 cells, respectively. In addition, it was found that LC-SNPs treated MCF-7 and HT-29 cells were arrested in the sub-G1 phase. Gene expression analysis indicated that the expression levels of the CASP3, CASP9, and BAX genes were elevated after treating MCF-7 and HT-29 cells with LC-SNPs. Further, SeNPs were observed to inhibit migration and invasion of MCF-7 and HT-29 cancer cells. The SeNPs, produced via L. casei, demonstrated strong anticancer effects on MCF-7 and HT-29 cells, suggesting their potential as biological agents in cancer treatment following additional in vivo experiments.

MicroRNA-155 is a main part of proinflammatory puzzle during severe coronavirus disease 2019 (COVID-19).

Genetic and epigenetic parameters play critical roles in determining the outcomes of the severe acute respiratory syndrome coronavirus type 19 (SARS-CoV-2) infection. MicroRNAs (miRNAs) are an important part of the epigenetic factors that regulate several functions of the immune cells and also viruses. Accordingly, the molecules can regulate expression of the immune cell proteins and virus in the host cells. Among the miRNAs, miRNA-155 (miR-155) is well-studied in patients suffering from severe coronavirus disease 2019 (COVID-19). It has been reported that the SARS-CoV-2 infected patients may be directed to induce a cytokine storm or severe proinflammatory responses. This review article discusses the pathological roles of miR-155 during COVID-19 infection.

MicroRNA-155 is a main part of proinflammatory puzzle during severe coronavirus disease 2019 (COVID-19)

Genetic and epigenetic parameters play critical roles in determining the outcomes of the severe acute respiratory syndrome coronavirus type 19 (SARS-CoV-2) infection. MicroRNAs (miRNAs) are an important part of the epigenetic factors that regulate several functions of the immune cells and also viruses. Accordingly, the molecules can regulate expression of the immune cell proteins and virus in the host cells. Among the miRNAs, miRNA-155 (miR-155) is well-studied in patients suffering from severe coronavirus disease 2019 (COVID-19). It has been reported that the SARS-CoV-2 infected patients may be directed to induce a cytokine storm or severe proinflammatory responses. This review article discusses the pathological roles of miR-155 during COVID-19 infection (AU)

MicroRNA-155 and 194 alter expression of Th17 and T regulatory-related transcription factors in the patients with severe coronavirus disease 2019 (COVID-19).

INTRODUCTION: It has been demonstrated that the patients with severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) suffer from severe inflammation. Due to the ethnics, the immune responses may be different. Additionally, microRNAs may alter immune responses in the patients. The current study was aimed to evaluate the expression of T helper subsets-related transcription factors, some T helper 17 (Th17) products, and two microRNAs, including miR-155 and miR-194, in the Iranian hospitalized patients. METHODS: In this study, T-box expressed in T cells (T-bet), GATA binding protein 3, The retinoid orphan receptor gamma t (RORγt), forkhead box P3 (FOXP3), interleukin (IL)-17A, IL-8, and CC ligand 20 (CCL20) mRNA levels and, miR-155 and miR-194 levels were evaluated in 70 patients suffered from severe coronavirus disease 2019 (COVID-19) and 70 healthy subjects using Real-Time qPCR technique. RESULTS: The findings showed that RORγt, and FOXP3 mRNA levels were significantly increased, while IL-17A, IL-8, and CCL20 mRNA levels were significantly decreased in the hospitalized SARS-CoV-2 infected patients. Although the levels of miR-155 and miR-194 were not different between groups, miR-194 has negative and positive correlations with RORγt and IL-17A in the Iranian healthy controls. CONCLUSION: This study reports although RORγt was up-regulated, IL-17A, IL-8, and CCL20 mRNA levels were significantly decreased in the hospitalized SARS-CoV-2 infected patients. It may be concluded that up-regulation of FOXP3, via development of T regulatory lymphocytes suppresses Th17 functions and neutralizes Th17 activities. MiR-194 may play crucial roles in regulation of RORγt and IL-17A expression in healthy people, the phenomenon that is disrupted in the severe SARS-CoV-2 infected patients.

Expression of MicroRNA-155 in Patients with Non-Hodgkin Lymphoma, Coronavirus Disease 2019, or Both: A Cross-Sectional Study.

Background: Non-Hodgkin lymphoma (NHL) is the eleventh leading cause of cancer-related death in the world. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL. Up to winter 2021-2022, the death toll caused by the coronavirus disease 2019 (COVID-19) has exceeded 5.6 million worldwide. Possible molecular mechanisms involved in the systemic inflammation, and cytokine storm in COVID-19 patients are still not fully understood. MicroRNA-155 (miR-155) plays a role in the post-transcriptional gene regulation of hematopoiesis, oncogenesis, and inflammation. The present study aimed to evaluate the expression of miR-155 in patients with DLBCL and/or COVID-19. Methods: A cross-sectional study was conducted from July to December 2020 in Tehran (Iran) to evaluate the expression of miR-155 in adult patients diagnosed with DLBCL and/or COVID-19. The real-time polymerase chain reaction technique was used to evaluate the expression of miR-155 in the sera of 92 adults who were either healthy or suffering from DLBCL and/or COVID-19. Relative quantification of gene expression was calculated in terms of cycle threshold (Ct) value. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The expression of miR-155 was not associated with the sex or age of the participants. In comparison with healthy individuals (-ΔCt -1.92±0.25), the expression of miR-155 increased in patients with COVID-19 (1.95±0.14), DLBCL (2.25±0.16), or both (4.33±0.65). Conclusion: The expression of miR-155 increased in patients with DLBCL and/or COVID-19.

Upregulation of Toll-Like Receptors 2, 5, 7, and 9 in the Cervical Epithelial Cells of Iranian Women Infected with High-Risk Human Papilloma Virus.

BACKGROUND: Toll-like receptors (TLRs) play dual roles against viruses, including defense against the viruses and induction of the viral-related cancers. High risk human papilloma viruses (HPVs) play key roles in induction of HPV-related cancers. The molecules that are upregulated by the high-risk viruses can be considered as the candidate to induce the cancers. This project was designed to evaluate expression of TLR1-9 in the women infected with HPV-high risk genotypes. METHODS: This project was performed on 40 women infected with high-risk HPV genotypes and 40 healthy controls. Infections with HPV-high risk genotypes and relative expressions of TLR1-9 were explored using real-time PCR technique. RESULTS: Relative expressions of TLR2, TLR5, TLR7, and TLR9 were significantly higher in the HPV-high risk genotype infected participants when compared to non-infected cases. CONCLUSIONS: Due to the results, it appears that TLR2, TLR5, TLR7, and TLR9 are more important than other TLRs in the pathogenesis of cancers in the Iranian women, who are infected with HPV-high risk genotypes.

TLR9 in the Human Papilloma Virus Infections: Friend or Foe?

Immune system plays dual roles during human papilloma virus (HPV) infections, from defense against the virus to induction or stimulation of the HPV-related cancers. It appears that various differences within the immune-related genes and the functions of the immunological parameters of the patients are the main factors responsible for the roles played by immune system during HPV infections. Toll-like receptors (TLRs) play key roles in the recognition of viruses and activation of immune responses. The molecules also can alter the target cell intracellular signaling and may participate in the transformation of the infected cells. TLR9 is the unique intracellular member of TLRs that recognize foreign DNA, including viral DNA. Thus, TLR9 may play significant roles in the defense against HPV and its related cancers. This review article discusses TLR9 antiviral and pathological roles during HPV infection.

Association of selected polymorphisms in GPX4, COMT, pre-miR-125a, pre-miR-10a, and pre-miR-323b genes in Iranian women with idiopathic recurrent pregnancy loss: A case-control study.

Background: Recurrent pregnancy loss (RPL) is a major concern among women worldwide. However, the exact mechanisms underlying miscarriage are not well understood. Recent evidence suggests that single nucleotide polymorphisms in various genes, especially miRNAs, may be responsible for RPL. Objective: We surveyed the association between polymorphisms in pre-miR-125a, pre-miR-10a, pre-miR-323b, GPX4, and GPX4 in Iranian women with idiopathic RPL. Materials and Methods: DNA was extracted from blood samples of 116 women with idiopathic RPL and 89 healthy women as controls who had previously had at least two successful pregnancies. Polymerase chain reaction was used for the amplification of the genes. Genotype screening along with SNaPshot were performed to detect different polymorphisms. Finally, the polymorphisms and frequency of each genotype were compared between the two groups. Results: The frequencies of polymorphisms in pre-miR-125a (p < 0.001) and pre-miR-10a (p = 0.04) were calculated among the case and control groups, which showed a statistical difference (p < 0.05), indicating an association between these polymorphisms and the symptoms of RPL. The frequencies of polymorphisms of genotypes in GPX4, COMT and pre-miR-323b did not demonstrate any difference between the two groups. Also, the amount of alleles in pre-miR-125a and pre-miR-10a were significantly different (p < 0.001 and p = 0.02, respectively) and the dominant inheritance model was proposed. Conclusion: In conclusion, pre-miR-125a and pre-miR-10a can be associated with RPL in women. The SNaPshot technique is a valuable tool to evaluate possible associations between polymorphisms and health conditions.

Expression of miRNA-601 and PD-L1 among Iranian Patients with Lung Cancer and Their Relationship with Smoking and Mycoplasma Infection.

OBJECTIVE: microRNAs (miRNAs) are highly conserved noncoding RNA molecules that mainly function to regulate gene expressions, and have a significant role in tumourigenesis. Programmed cell death-ligand 1 (PD-L1) is a major co-inhibitory checkpoint signal that controls T cell activities, maintains peripheral tolerance and is contribute to the development of cancer. The aim of this study is to examine miRNA-601 and PD-L1 gene expression in patients with non-small-cell lung cancer (NSCLC) and its relation with Mycoplasma infection. MATERIALS AND METHODS: In this case-control study, respiratory secretions and blood samples were collected from 80 healthy people and 80 NSCLC patients. The expression levels of miRNA-601 and PD-L1 were evaluated using real-time polymerase chain reaction (qRT-PCR). The presence of Mycoplasma species in respiratory secretions was detected by biochemical assays and PCR. RESULTS: There was no significant difference in the expression level of miRNA-601 between control and patients with tumour stage I, but miRNA-601 expression was significantly downregulated in patients with tumour stages II, III, and IV (P<0.05). A significant, negative relationship was found between miRNA-601 expression and tumour stage (P<0.001). Overexpression of PD-L1 was found in all of the disease stages. PCR results showed the presence of Mycoplasma pneumoniae (M. pneumoniae) in respiratory secretions from patients with stages III and IV NSCLC. We observed that 72% of patients with stages III and IV NSCLC had a positive smoking history and 65.3% were positive for Mycoplasma. CONCLUSION: Serum miRNA-601 may act as a potential noninvasive biomarker for lung cancer and Mycoplasma infection prognosis.

Classification and identification of human papillomavirus based on its prevalence and development of cervical lesion among Iranian women.

Introduction: Cervical cancer is the most common female cancer in large areas of the developing world, and almost half of these cases (54%) arises in Asia, where cervical cancer is still threatening women's health and survival, which makes it a considerable public problem. Human papillomavirus (HPV) is one of the most powerful human carcinogens. Today, it has been proven that all cervical cancers and primary precancerous lesions are caused by carcinogenic types of HPV infections. HPV genotyping can therefore evaluate the screening programs. Methods: Five hundred fifty women referring to the gynecological centers were subjected to Pap smear cell samples. The cytopathological diagnosis of obtained cervical samples was based on the Bethesda system. HPV genotyping was carried out using the INNO-LiPA HPV Genotyping Extra II Amp assay. Results: In a total of 244 HPV positive cases, single­type HPV infec-tion was observed in 49.6%, while multi­type HPV infections (including ≥ 2 types) were found in 45.5% of cases. Among the 110 cases with abnormal cytology results, going-over analyses led to the identification of atypical squamous cell of unknown significance (ASCUS) in 73 cases, low­grade squamous intraepithelial lesions (LSIL) in 24 cases, and high­grade squamous intraepithelial lesion (HSIL) in 12 cases. In these groups, the infection rate of high-risk HPV (HR-HPV) was 89%, 82%, and 100%, respectively. Conclusion: In this study, the total population of women suffering from different cervical lesions and malignancy was found to be infected with various HPV genotypes. High prevalence of HPV- 53 and HPV- 16 detected among participants with normal cytology can be considered as a tip-off development of cervical cancer among Iranian women.

Genotypic and phenotypic characterisation of clinical isolates of methicillin-resistant Staphylococcus aureus in two different geographical locations of Iran.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has become more prevalent all over the world and it is important to determine MRSA prevalence and typing in different regions. The present study was carried out to determine the prevalence and frequency of circulating molecular types of MRSA isolates as well as their antibiotics susceptibility in Tabriz and Kerman cities of Iran. Materials and Methods: A total of 230 S. aureus isolates were collected from Tabriz (n=125) and Kerman (n=105) during January to December 2018. MRSA isolates were identified by PCR amplification of nuc and mec A genes. Antibiotic susceptibility of MRSA isolates were determined by Kirby-Bauer disk diffusion method. Multiplex PCR was exploited to detect various types of SCCmec. Results: The MRSA prevalence was 51/125 (40.8%) in Tabriz and 60/105 (57.1%) in Kerman. Overall, 36/51 (70.58%) and 15/51 (29.41%) isolates and 37/60 (61.66%) and 23/60 (38.34%) isolates were isolated from inpatients and outpatients in Tabriz and Kerman, respectively. Almost all of the isolates were resistant to penicillin and all of them were sensitive to linezolid. Thirty five (68.2%) and 34(56.6%) of MRSA isolates in Tabriz and Kerman were determined as MDR, respectively. SCCmec typing showed that the frequent SCCmec type in both Tabriz and Kerman cities was SCCmec III (56.86% and 55%, respectively). Conclusion: The high prevalence of MRSA makes it necessary to revisit the antibiotics administration by physicians. Indeed, periodic evaluation of antibacterial susceptibility patterns of the MRSA strains is required for efficient treatment of MRSA infections.

Pseudomonas aeruginosa quorum sensing modulates immune responses: An updated review article.

Pseudomonas aeruginosa is an opportunistic bacterium which induces some complications in immunocompromised patients. Pseudomonas aeruginosa is a quorum-sensing using bacterium which regulates its genes expression. The bacterium uses two famous pathways for quorum sensing entitled LasI/LasR and RhlI/RhlR systems. It has been documented that the bacteria which use quorum sensing are able to overcome immune responses. This review article aims to present recent information regarding the effects of Pseudomonas aeruginosa quorum sensing systems on the host immune responses.

Tumor growth factor-ß is an important factor for immunosuppression and tumorgenesis in Polyoma BK virus infection; a systematic review article.

Polyoma BK virus (PBK) is a prevalent human specific virus and the cause of several malignancies in human. The main mechanisms used by PBK to induce/stimulate human cancers are yet to be clarified but it has been proposed that PBK may use several mechanisms to induce/stimulate cancers in human including attenuation of immune responses via up-regulation of immunosuppressor molecules. Transforming growth factor beta (TGF-ß) is a key multifunctional factor from modulation of immunosurveillance to angiogenesis. The key roles of TGF-ß in the progression of Th17 and T regulatory subsets, the most important immune cells involved in development of cancers, have been demonstrated. Thus, this review article aims to describe the mechanisms used by PBK in induction/stimulation of human cancers in TGF-ß dependent manner..

Isolation and Identification of Mycoplasma synoviae From Suspected Ostriches by Polymerase Chain Reaction, in Kerman Province, Iran.

BACKGROUND: Mycoplasma synoviae is an important avian pathogen which can cause both respiratory disease and synovial joint inflammation (synovitis) in poultry. Mycoplasmas spp. may cause the respiratory system infection in ostriches with symptoms such as inflammation of the nose, trachea and also damages of lungs. OBJECTIVES: The current study aimed to use the M. synoviae specific Polymerase Chain Reaction (PCR) and microbiological methods in order to isolate and identify M. synoviae from suspected ostriches in Kerman Province, Iran, and compare the two methods (microbiological and PCR) employed to confirm Mycoplasmal contamination of ostrich lungs. MATERIALS AND METHODS: Fifty three samples of different parts of lung and trachea were immediately collected after slaughtering the ostriches in Kerman Province six months. Samples were cultured in the same conditions in pleuropneumonia-like organism (PPLO) broth and to isolate and identify M. synoviae, PCR and microbiological methods were conducted. The identified isolates were confirmed by specific amplification of 16S rRNA gene (163 and 207 base pair). RESULTS: In the current study, 25 and 17 out of 53 ostrich samples were identified as Mycoplasma-positive in the PCR and microbiological methods, respectively; and 13 out of 25 the mentioned Mycoplasma-positive samples were also confirmed by PCR method. CONCLUSIONS: The current study showed that PCR method is time consuming, effective, and efficient method to detect M. synoviae infection in ostriches. PCR method could be recommended as an alternative for culturing; M. synoviae was isolated from ostriches for first time in Kerman Province, Iran.

Isolation and molecular identification of mycoplasma genitalium from the secretion of genital tract in infertile male and female.

BACKGROUND: Mycoplasmas can cause acute and chronic diseases at multiple sites with wide-range complications and have been implicated as cofactors in diseases. The infections influenced form genital mycoplasmas specifically Mycoplasma hominis and Mycoplasma genitalium potentially affect reproductive disorders, and infertility. OBJECTIVE: Isolation and molecular identification of Mycoplasma genitalium from the genital tract of infertile male and vaginal discharge of infertile female referred to Infertility Center of Kerman in 2013. MATERIALS AND METHODS: This study was a randomized, prospective study. We included 100 infertile male and 100 infertile female that were referred to the Infertility Center of Kerman. Then for isolation and molecular identification of Mycoplasma genitalium from urethral and vaginal discharge polymerase chain reaction was performed on Mycoplasma genus and genitalium. RESULTS: From a total of 100 semen samples 45 patients (45%) were mycoplasma-positive and 13 (28.8%) were genitalium species positive. Also, from a total of 100 women samples 43 women (43%) were mycoplasma-positive and 10 (23.2%) were genitalium species positive. Positive samples were sequenced and phylogenetic tree was drawn. CONCLUSION: According to the results of this study, a high percentage of infertile male and female were infected with the Mycoplasma genitalium. For prevention of harmful and significant consequences of this infection, we suggest a screening program in symptomatic infertile couples.

Isolation and molecular identification of Mycoplasma hominis in infertile female and male reproductive system.

BACKGROUND: Infection of urogenital system with Mycoplasma potentially affect reproductive system and increases infants mortalities. Therefore, detection of these organisms is an important issue that should be considered and appropriate diagnostic methods should be used to identify these microorganisms. In the female reproductive system, infection can affect different parts of the cervix, endometrium, and fallopian tube. The extent of this infection in different diseases and its pathogenesis might be related to anatomic site of involvement. Some infections can lead to infertility in both males and females. Genital infection with Mycoplasmas have devastating effects on reproductive organs and cause fertility disorders and mortality in infants. In recent years, many studies have been conducted to isolate these pathogens; however, the isolates have not been identified so far. OBJECTIVES: The aim of this study was to determine the molecular identity of Mycoplasma hominis isolated from infertile female and male reproductive system in the Infertility Center of Kerman. MATERIALS AND METHODS: This descriptive study was performed purposefully on 100 infertile females and 100 infertile males who were referred to the Infertility Center of Kerman during a six-month period. The collected samples of semen and vaginal swabs were examined for the presence of M. hominis by PCR. The samples with positive results in PCR were selected for molecular identification. Alignment of samples sequence was performed using MEGA 5 software through Neighbor-joining method. RESULTS: Among 100 samples from infertile males, the presence of genus Mycoplasma was confirmed in 45 cases of which 15 cases were infected with M. hominis. Among 100 samples from infertile female, the presence of genus Mycoplasma was confirmed in 43 cases of which 18 case were infected with M. hominis. The positive samples were sequenced and the phylogenetic tree was plotted. CONCLUSIONS: The results showed that 37.5% of infertile males and females were infected with M. hominis. Analysis of the nucleotide sequences of the study isolates indicates a particular variety among these isolates. In comparing the isolates in the study, a very little genotypic similarity was found among some of them.