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Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, the underlying epigenetic mechanisms governing endothelial cell behavior in this context remain poorly understood. To address this knowledge gap, we conducted in vitro experiments using human umbilical vein endothelial cells subjected to various tensional forces simulating pathophysiological blood flow shear stress conditions, ranging from normotensive to hypertensive forces. Our study uncovers a noteworthy observation wherein endothelial cells exposed to high shear stress demonstrate a decrease in the epigenetic marks H3K4ac and H3K27ac, accompanied by significant alterations in the levels of HDAC (histone deacetylase) proteins. Moreover, we demonstrate a negative regulatory effect of increased shear stress on HOXA13 gene expression and a concomitant increase in the expression of the long noncoding RNA, HOTTIP, suggesting a direct association with the suppression of HOXA13. Collectively, these findings represent the first evidence of the role of histone-related epigenetic modifications in modulating chromatin compaction during mechanosignaling of endothelial cells in response to elevated shear stress forces. Additionally, our results highlight the importance of understanding the physiological role of HOXA13 in vascular biology and hypertensive patients, emphasizing the potential for developing small molecules to modulate its activity. These findings warrant further preclinical investigations and open new avenues for therapeutic interventions targeting epigenetic mechanisms in hypertensive conditions.
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Epigênese Genética , Histonas , Humanos , Histonas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hemodinâmica , Estresse Mecânico , Células CultivadasRESUMO
Introduction: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. Materials and methods: Ligand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes. Results and discussion: We evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.
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The first-generation antihistamine chlorpheniramine (CPA) is believed to have both anxiolytic and antidepressant properties. The current study sought to assess the mechanisms behind the antidepressant and anxiolytic effects of CPA therapy concerning oxidative stress, inflammation, and nuclear factor p45 for erythroid 2-Brain-derived neurotrophic factor (Nrf2-BDNF) signaling pathway in forced swimming-induced depressive-like behavior and anxiety. Eighteen male Wistar rats (180-200 gm) rats were separated into three groups (n = 6): a stressed group (acute stress) that underwent the forced swimming test (FST) and a stressed group that received pretreatment with CPA (10 mg/kg body weight) for 3 weeks (CPA + acute stress). Animals were subsequently put through the following behavioral tests after undergoing a forced swim test (FST) for 5 min: an immobility test, open field test, and elevated plus maze test. Serum cortisol levels were measured when the rats were euthanized at the end of the experiments. Brain neurotransmitters (cortisol, serotonin, and noradrenaline), oxidative stress (SOD and MDA), inflammatory (IL-6 and IL-1) biomarkers, and the Nrf2-BDNF signaling pathway in the hippocampus and cerebral cortex tissues was determined. CPA prevented stress-induced increases in cortisol levels (p < 0.0001), decreased brain neurotransmitters, and increased oxidative stress and inflammation. CPA also upregulated the Nrf2-BDNF signaling pathway. Thus, CPA mitigates depressive-like behavior and anxiety by inhibiting oxidative stress and inflammation and upregulating the Nrf2-BDNF signaling pathway in the brain tissues.
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Background: Redox homeostasis is the vital regulatory system with respect to antioxidative response and detoxification. The imbalance of redox homeostasis causes oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis. Nrf2/Keap1 signaling is reported to be involved in cancer cell growth and survival. A high level of Nrf2 in cancers is associated with poor prognosis, resistance to therapeutics, and rapid proliferation, framing Nrf2 as an interesting target in cancer biology. Sirtuins (SIRT1-7) are class III histone deacetylases with NAD + dependent deacetylase activity that have a remarkable impact on antioxidant and redox signaling (ARS) linked with Nrf2 deacetylation thereby increasing its transcription by epigenetic modifications which has been identified as a crucial event in cancer progression under the influence of oxidative stress in various transformed cells. SIRT6 plays an important role in the cytoprotective effect of multiple diseases, including cancer. This study aimed to inhibit SIRT6 using an imidazole derivative, Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate, to assess its impact on Nrf2/Keap1 signaling in A549 and NCI-H460 cell lines. Method: Half maximal inhibitory concentration (IC50) of Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate was fixed by cell viability assay. The changes in the gene expression of important regulators involved in this study were examined using quantitative real-time PCR (qRT-PCR) and protein expression changes were confirmed by Western blotting. The changes in the antioxidant molecules are determined by biochemical assays. Further, morphological studies were performed to observe the generation of reactive oxygen species, mitochondrial damage, and apoptosis. Results: We inhibited SIRT6 using Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate and demonstrated that SIRT6 inhibition impacts the modulation of antioxidant and redox signaling. The level of antioxidant enzymes and percentage of reactive oxygen species scavenging activity were depleted. The morphological studies showed ROS generation, mitochondrial damage, nuclear damage, and apoptosis. The molecular examination of apoptotic factors confirmed apoptotic cell death. Further, molecular studies confirmed the changes in Nrf2 and Keap1 expression during SIRT6 inhibition. Conclusion: The overall study suggests that SIRT6 inhibition by imidazole derivative disrupts Nrf2/Keap1 signaling leading to oxidative stress and apoptosis induction.
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Previous studies have demonstrated the beneficial effects of melatonin in diabetic rats. However, limited studies have been conducted on the potential effects of melatonin on the descriptive histopathological and morphometric findings in different compartments of the adrenal glands in diabetic animal models. In this study, using a streptozotocin (STZ)-induced diabetic rat model, we sought to examine histological alterations in the pancreas and adrenal glands and observe the effect of the administration of melatonin on the histopathology and morphology of the pancreas and the adrenal gland cortex and medulla that are altered by STZ-induced hyperglycemia. Rats were randomly assigned to four different groups: Group I, normal control; Group II, melatonin group (MT) (10 mg/kg/day); Group III, (diabetic STZ group), and Group IV, diabetic (STZ) + melatonin group (MT). Throughout the experiment, the animals' fasting blood sugar levels were measured. Blood was obtained to determine the animals' cumulative blood sugar levels after sacrification. For histological and morphometrical evaluations, the pancreatic and adrenal gland tissues were dissected and processed. Our results showed that diabetic rats receiving melatonin significantly (P < 0.05) improved their fasting blood sugar and cumulative blood sugar levels compared to the diabetic group not receiving melatonin. Furthermore, histopathological examinations of the pancreatic and adrenal tissues of the diabetic rats indicated the occurrence of severe histopathological and morphometric changes. Morphometric analysis of the adrenals indicated a significant increase (P < 0.05) in the thickness of the cortex zones [zona glomerulosa (ZG), zona fasciculata (ZF), and zona reticularis (ZR)] for the diabetic STZ group compared with other groups, and a significant decrease (P < 0.05) in the diameter of the in adrenal gland medullas in the diabetic STZ rats compared to the other groups. Furthermore, treatment with melatonin restored these changes in both the pancreatic and adrenal gland tissues and produced a significant (P < 0.05) improvement in the cortex and medulla thickness compared to the untreated diabetic rats. Overall, melatonin significantly reduced the hyperglycemic levels of glucose in diabetic rats and reversed the majority of histopathological alterations in the tissues of the pancreas and adrenals, demonstrating its anti-diabetic activity.
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Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a global and evolving pandemic associated with heavy health and financial burdens. Considering the oral cavity as the major reservoir for SARS-CoV-2, a systematic review and meta-analysis were conducted to assess the efficacy of mouth rinses and nasal sprays in reducing the salivary viral load of SARS-CoV-2. All in vivo and in vitro studies that assessed the virucidal efficacy of mouth rinses and nasal sprays against SARS-CoV-2 and were published in the English language from December 2019 to April 2022 were considered for analyses. Special Medical Subject Headings terms were used to search Pubmed, Scopus, Embase Ovid, and Web of Science databases. The toxicological data reliability assessment tool (ToxRToool) was used to assess the quality of the included studies. Thirty-three studies (11 in vivo and 22 in vitro) were deemed eligible for inclusion in this analysis. Results of the pooled data showed that povidone-iodine is the most efficacious intervention in vivo in terms of reducing the SARS-CoV-2 salivary viral load, followed by chlorhexidine. The mean difference in the viral load was 86% and 72%, respectively. Similarly, povidone-iodine was associated with the highest log10 reduction value (LRV) in vitro, followed by cetylpyridinium chloride, (LRV = 2.938 (p < 0.0005) and LRV = 2.907 (p = 0.009), respectively). Povidone-iodine-based oral and nasal preparations showed favourable results in terms of reducing SARS-CoV-2 viral loads both in vivo and in vitro. Considering the limited number of patients in vivo, further studies among larger cohorts are recommended.
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COVID-19 , SARS-CoV-2 , Cetilpiridínio , Clorexidina , Humanos , Antissépticos Bucais/farmacologia , Sprays Nasais , Povidona-Iodo/farmacologia , Reprodutibilidade dos TestesRESUMO
Candida is a commensal yeast. It can be infective when the host's defense mechanism is weakened, as in the case of squamous cell carcinoma patients. We aimed to evaluate the prevalence and clinical mycological manifestation of candidiasis in 150 cancer cases comprised of preoperative and post-operative (with or without radiotherapy) upper aerodigestive squamous cell carcinoma. A total of 150 patients suffering from squamous cell carcinoma of the Upper Aero-Digestive Tract (UADT) were divided into preoperative (n = 48), post-operative without radiotherapy (n = 29) and post-operative with radiotherapy (n = 73). Samples were collected using cotton swabs and cultured. Candida species were identified according to color pigmentation on Candida Differential Agar (CDA) plate. The clinico-mycological association of patients was evaluated by the chi-square test, and 98 out of 150 patients showed the presence of various Candida species. The major species isolated was Candida albicans (53%), followed by Candida tropicalis (16%). There was a significant statistical difference between patients who showed mycological associations and patients who did not have any such association (p = 0.0008). The prevalence of oral candidiasis was found to be 65.33% among total cases of upper aero-digestive squamous cell carcinoma. Chronic erythematous cases of candidiasis were mainly seen in preoperative squamous cell carcinoma cases, whereas the acute erythematous type of candidiasis was mainly seen in post-operative cases who received radiotherapy. The clinicomycological assessment can help to correlate the signs and symptoms with the presence of candidiasis in upper aerodigestive squamous cell carcinoma patients. Meticulous testing and examination can help in the early detection of candidiasis. Future studies are needed to develop advance scientific preventive strategies for high-risk cases.
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Candidíase Bucal , Candidíase , Carcinoma de Células Escamosas , Candida , Candida albicans , Candidíase/complicações , Candidíase/diagnóstico , Candidíase/epidemiologia , HumanosRESUMO
microRNA (miRs or miRNAs) is a type of non-coding RNA which plays the role of a regulator in gene expression. A number of miRNAs has been found by the researchers for its critical role in the pathogenesis of polycystic ovary syndrome (PCOS). But there is a no clear information available about the biological role played by miR-21 in PCOS prognosis. So, the aim of the current study is to determine the role played by miR-21 in the progression of PCOS. In order to achieve this aim, the researcher examined miR-21 expression levels in ovarian tissue samples collected from PCOS patients as well as their KGN cells (human granulosa-like tumor cell line). The study results inferred downregulation in the expression levels of miR-21 in ovarian tissues of PCOS patients and KGN cells, when compared with unaffected ovarian tissues and IOSE80 (human ovarian surface epithelial cell line). With the overexpression of miR-21, the proliferation of KGN cells was prevented and apoptosis was induced among these cells. The authors used StarBase analysis for predicting the direct binding target of miR-21. As per the assay results attained from luciferase reporter assay and western blot analysis, it was found that SNHG7 acted as a target gene for miR-21 while the latter downregulated the former. To conclude, the current study revealed the contribution of miR-21/SNHG7 axis in the regulation of Granulosa Cell (GC) proliferation and apoptosis. It further suggested a new molecular mechanism for GC dysregulation while the finding presents a new promising target for PCOS treatment procedure.
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Células da Granulosa/patologia , MicroRNAs/metabolismo , Síndrome do Ovário Policístico/genética , Insuficiência Ovariana Primária/genética , RNA Longo não Codificante/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Insuficiência Ovariana Primária/patologia , RNA Longo não Codificante/metabolismoRESUMO
INTRODUCTION: HOXB8 is a protein that was found to promote cancer proliferation and invasion. ILK is a protein kinase which has a role in carcinogenesis. FAT4 is a tumor homologue that has a role in EMT and autophagy regulation. AIM OF THE STUDY: To identify expression of Human HOXB8, Integrin-linked kinase (ILK1) and FAT homolog 4 (FAT4) in colorectal cancer (CRC) correlating their expression with pathological, prognostic and clinical parameters of CRC. MATERIAL AND METHODS: We assessed the expression of HOXB8, ILK and FAT4 in fifty CRC patients and ten samples from nearby non-neoplastic colonic mucosa using immunohistochemistry. RESULTS: The expression of HOXB8 and ILK in CRC was positively associated with high tumor grade, advanced tumor stage, lymph node involvement (p < 0.001), occurrence of distant metastases (p = 0.003 and 0.024 respectively), higher incidence of tumor recurrence (p = 0.03, p < 0.001 respectively), worse survival rates (p = 0.038 and 0.003 respectively). The expression of FAT4 in CRC was correlated with lower grade, early stage of the tumor, absence of lymph node involvement (p < 0.001) and lack of distant metastases (p = 0.011). High FAT4 expression was associated with absence of tumor recurrence (p < 0.001) and favorable survival rates (p < 0.001 and 0.003). CONCLUSIONS: High immunohistochemical expression of HOXB8 and ILK in addition to low immunohistochemical expression of FAT4 was associated with unfavorable prognostic and pathological parameters of CRC.
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OBJECTIVE: Transcription factor activating protein 2 B (TFAP2 B) is a transcription factor that regulates many steps of embryogenesis, cell growth, apoptosis and recently oncogenesis and cancer progression. AP-1 is a transcription factor that is a downstream molecule of the MAPK signaling pathway. Juxtaposed with zinc finger gene 1 (JAZF1) is a recently detected transforming growth factor which has a role in carcinogenesis. Hence the present study aimed to assess those markers expression in tissues from patients with such cancer correlation their expression with clinic-pathological findings of the tumor and prognostic and follow-up findings of patients. METHODS: We have collected tissue samples from papillary thyroid cancer patients and adjacent non-neoplastic tissues from 80 patients. We assessed the expression of TFAP2B, AP-1 and JAZF1 using immunohistochemistry. RESULTS: Expression of TFAP2B was positively associated with lymph nodes metastases (p=0.003), distant metastases (p=0.002), recurrence of the tumor (p=0.002), unfavourable disease-free survival rate (p=0.003). AP-1 expression is positively associated with advanced stage (p=0.002), presence of extra-thyroid invasion (p=0.005), recurrence of the tumor (p=0.005), unfavorable disease-free survival rate (p=0.01). JAZF1 expression is negatively associated with huge tumor size (0.023), vascular invasion (p=0.007) and unfavorable overall survival rate (p=.030). CONCLUSION: High expression levels of TFAP2B and AP-1 and low expression levels of JAZF1 were associated with unfavourable pathological, prognostic parameters and dismal patient's outcome.
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Biomarcadores Tumorais/metabolismo , Proteínas Correpressoras/metabolismo , Proteínas de Ligação a DNA/metabolismo , Recidiva Local de Neoplasia/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-2/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
INTRODUCTION: Triple-negative breast cancer (TNBC) is a markedly aggressive molecular subtype of breast cancer; there is an urgent need to clarify the molecular mechanisms underlying the progression and metastases of BLBC, in order to find a novel targeted therapy. Microfibrillar-associated protein 5 (MFAP5) plays an essential role in the regulation of cell behaviour and survival. Integral membrane protein 2A (ITM2A) is a type II transmembrane protein, which is a member of a family of autophagy related proteins.The aim of this study was to assess the expression of MFAP5 and ITM2A proteins in tissues of BLBC using immunohistochemistry, in order to correlate the expression with clinicopathological and prognostic parameters of such aggressive cancer. MATERIAL AND METHODS: The present study included sections from archived paraffin blocks retrieved from 120 patients with TNBC. We collected cases from three years, i.e. from 2016 to 2019. We assessed expression of MFAP5 and ITM2A using immunohistochemistry. RESULTS: High expression of MFAP5 and low expression of ITM2A was associated with advanced stage (p = 0.007), higher grade of tumour (p = 0.005 and p = 0.004, respectively), the presence of lymph nodes metastases (p < 0.001 and p = 0.002, respectively), lower three-year RFS rate (p < 0.001 and p = 0.016, respectively), and lower three-year OS rate (p < 0.001). CONCLUSIONS: MFAP5 and ITM2A are novel prognostic biomarkers for breast cancer and might be considered as promising therapeutic targets for patients with breast cancer, particularly TNBC molecular subtype, in the future.
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Aim: HPV is an important cause of cervical cancer, but Chlamydia trachomatis (CT) is suspiciously involved in this disease ranging from direct to its involvement as a cofactor with HPV. We performed this study to understand the interaction of HPV and C. trachomatis with humans and its contribution to cervical cancer. Materials & methods: Host-pathogen and pathogen-pathogen protein-protein interaction maps of HPV/CT/human were prepared and compared to analyze interactions during single/coinfection of C. trachomatis and HPV. The interacting human proteins were detected by their involvement in cervical cancer. Results:C. trachomatis may interact with several cancer associated proteins while HPV and C. trachomatis largely interact with different human proteins, suggesting different pathogenesis. Conclusion:C. trachomatis coinfection with HPV may modulate cervical cancer development.
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Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/metabolismo , Papillomaviridae/metabolismo , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/metabolismo , Infecções por Chlamydia/metabolismo , Chlamydia trachomatis/genética , Coinfecção/metabolismo , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/metabolismo , Ligação Proteica , Mapas de Interação de Proteínas , Proteômica , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/virologiaRESUMO
The associations of individualistic versus collectivistic value orientations with suicidal ideation and attempts, attitudes towards suicide and towards suicidal individuals, and psychological distress were investigated across 12 nations (N = 5572 university students). We expected differential associations of value orientations with suicidal behavior and moderating effects of the prevailing value orientations in the various countries. Findings showed that intermediate levels of individualism appeared protective against suicide attempts across all investigated nations, but that, otherwise, there seemingly are no universal associations of individualism and collectivism with suicidal behaviors. High collectivism was associated with less suicidal ideation only in individualistic countries. Low individualism appeared to be a risk factor for suicidal ideation specifically in Muslim collectivistic cultures, whereas high individualism in Asian collectivistic cultures. Collectivistic values are uniformly associated with less permissive attitudes to suicide, whereas individualistic values with a more stigmatized view of suicidal behavior. Both individualistic and collectivistic values were associated with socially accepting attitudes to a suicidal peer, helping a suicidal friend, and emotional involvement. The associations of individualistic and collectivistic values with disapproving attitudes to suicidal disclosure were complex. Beliefs in punishment after death for suicide, seeing suicide as mental illness, and emotional involvement with a suicidal friend were lower in high-suicide-rate countries. These evidence patterns are discussed in the light of related research evidence, along with directions for future research in this area.
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BACKGROUND: Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. This study aimed to address the preventive procedures to protect healthcare workers at hospital to avoid COVID-19, and infection control procedures to protect dental professionals in dental office. METHODS: We conducted a search of published articles from PubMed, google scholar databases using key words such as COVID-19, healthcare worker, infection control, and dental practice. Relevant articles were identified and reviewed. Most published papers were clinical reports and case studies. We have selected some of the current published papers written in English in 2020. RESULTS: Infection control procedures to protect health workers at hospitals, and dental professionals at dental office were summurised and presented. Infection control procedures for healthcare workers at hospitals include Personal protective equipment, Korea filter (KF)94 respirator, goggles, face protector, disposable waterproof long-arm gown, and gloves, and others. Extra-protection procedures should be taken with old and vulnerable healthcare workers. Dental professionals should evaluate patients in advance before starting dental treatment. Aerosols generating procedures should be avoided and personal protective equipment should be used. Dental treatment should be restricted to emergency cases only. CONCLUSION: Old medical staff should be in safer distance to avoid infection, but young physicians and nurses should work at frontline as their immunity is better than their colleagues at old age. Screening patients and measurement of the body temperature are essential measures before dental treatment.
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COVID-19/prevenção & controle , Consultórios Odontológicos , Odontólogos , Hospitais , Controle de Infecções/métodos , Recursos Humanos em Hospital , Adulto , Fatores Etários , Idoso , Odontologia , Guias como Assunto , Pessoal de Saúde , Humanos , Pessoa de Meia-Idade , Equipamento de Proteção Individual , SARS-CoV-2RESUMO
BACKGROUND: This cross-sectional cohort study aimed to assess the associations between the serum uric acid levels and oral leukoplakia (OL), submucous fibrosis (OSMF) and squamous cell carcinoma (OSCC), and to correlate these with the clinical and histopathological features of these lesions. METHODS: Fifty-two patients with oral potentially malignant disorders (OPMD) (25 OL and 27 OSMF cases) and 33 OSCC patients with complete clinical and histopathological characteristics were included. A healthy control group was also investigated. The serum uric acid concentration was assessed using the uricase method from a blood sample without hemolysis. RESULTS: The level means of serum uric acid in the OL, OSMF and OSCC patients were 3.86±1.31, 5.65±0.85 and 4.99±1.34 mg/dL, respectively, compared to 5.16±0.97 mg/dL in the healthy controls. CONCLUSIONS: The serum uric acid levels were reduced in the OL and OSCC patients but they were increased in the OSMF patients when compared to the healthy controls. No significant differences were seen in the clinical and histopathological features of the OL and OSMF patients. Future studies with larger sample sizes may improve the understanding of the contributory role of uric acid in the risk stratification of OPMDs. Although measuring the serum uric acid level involves a simple and economical assay, the data from this cross-sectional cohort does not support the clinical utility of evaluating the uric acid levels in OPMD and OSCC patients.
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Gastric cancer is classified to be an aggressive disease with poor treatment outcome, as most cases remain undetected until later stages, wherein surgery and few chemotherapeutics become the only recommended treatment course. The process of cancer development is multistep involving many stages and types of precancerous lesions, and hence, routine monitoring becomes a necessity in those detected with these or exposed to risk factors. Studying the pattern of gastric cancer for any geographical region is also important to control mortality and focus on implementation of efficient management and treatment guidelines. The cause for gastric cancer can be genetic, racial as well as environmental, and hence the pattern of this malignancy differs across geographical regions and between the developing and the developed nations. In case of the Kindgom of Saudi Arabia, very few hospital-based reports have been published highlighting the pattern of gastric cancer, and the associated incidence and mortality rates. However, classified to be one of the most crucial cancer forms in Saudi Arabia, research pertaining to epidemiology, presentation and pathological features are limited. Studying gastric cancer occurrence from public health viewpoint is important also because eradication of causative agents like those that H. pylori has also shown been not reduce the risk of cancer development among individuals with atrophic metaplastic gastritis. In case of Saudi Arabia, many inherent risks for this malignancy exists like waterpipe smoking and shift in diet pattern from the traditional Mediterranean diet. Our review focusses on pattern of gastric cancer on a global scale in comparison to scenario in Saudi Arabia. The aim is to encompass all of the less stressed upon facts about this malignancy in the Kingdom, paving way for future work in this regards.
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BACKGROUND: There are reports of non-toxigenic C. difficile strains from asymptomatic carriers are increasing source of transmission. Asymptomatic carriage transmission in the hospital or community settings might have changed over the years. Therefore, we initiated a prospective epidemiological study to define the risk factors and pathogenicity of asymptomatic C. difficile carriage. METHODS: Stools sample from 188 subjects with diarrhoea due to C. difficile toxin and colonization without diarrhoea was subjected to routine microbial culture, molecular characterization for identification of toxin genes and mechanisms of resistance in C.difficile. Demographic data were recorded. Fifty five were positive for C. difficile includes thirty nine toxigenic C. difficile (TCD) and sixteen non toxigenic C. difficile (NTCD) isolates. Pathogenecity of toxic and nontoxic strains were analysed using AO/EB staining, Annexin V staining using flow cytometer and Galleria mellonella survival analyses. RESULTS: Among 188, fifty five were positive for C.difficile. Infected or colonized individual with TCD or NTCD were more frequently exposed to hemodialysis compared with uncolonized patients. Isolates showed more resistant to clindamycin and levofloxacin. All TCD and eight of NTCD were tcdA-positive. Only four of TCD were positive for cdtA, tcdA, and tcdB (7%, nâ¯=â¯55). In thirty isolates erm (B) gene was found to be prevelant gene. High virulence was found with TCD strain and it was validated using in Galleria mellonella infection model which supported in vitro experiments. The strain with cdtA, tcdA, and tcdB, seen to have elevated virulence to increased resistance and virulence subsequently led to raised virulence in this pathogen. CONCLUSION: Asymptomatic TCD colonization was relatively high, however, with a small number of enrolled subjects the significant of results might have limitations and the occurrence of CDI among different age group still remains unclear.
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Toxinas Bacterianas/genética , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Epidemiologia Molecular , ADP Ribose Transferases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Clindamicina/farmacologia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/patogenicidade , Infecções por Clostridium/microbiologia , Diarreia/epidemiologia , Diarreia/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterotoxinas/genética , Fezes/microbiologia , Feminino , Genes Bacterianos/genética , Humanos , Levofloxacino/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Virulência/genética , Adulto JovemRESUMO
BACKGROUND: Since the majority of morphological changes evaluation of myocardium in ischaemic heart disease was in animal model, we detected the importance to evaluate such changes in human patients to gain insights into the targets of cellular damage and to reconcile or refine those experiments. METHODS: Tissue sections from left atrial appendage of the heart were carefully dissected from seventy five patients underwent conventional coronary artery bypass grafting at the cardiothoracic surgical department, Manchester Royal Infirmary. Tissue was fixed, sectioned, stained and six random sections were photographed and the images were assessed and quantified using Image Analyser Pro-Plus software, version 4.1. Arterioles, venules, intermediate sized vessels, and capillaries were directly counted within the highlighted area of myocardium under LM. Ultra-thin sections were imaged in a Tecnai 12 Biotwin transmission electron microscope at a magnification of ×4200 and photographed by a camera with a black and white film to quantify different structures of myocardium. RESULTS: The arteriole wall to lumen ratio was significantly increased in ischaemic heart disease patients 18.57 ± 2.89 compared to controls 8.3 ± 1.57, (P < 0.01). The regression analysis between vascular density and cardiomyocyte size demonstrated a significant inverse correlation between transverse cardiomyocyte diameter and arteriole, capillary and total vessel density (P < 0.01, 0.04, 0.02), respectively. Lumen area of the distal myocardial capillary was significantly reduced in IHD patients compared to controls (P < 0.01). CONCLUSION: These results elucidate the morphological changes in the myocardial microvasculature of patients with ischaemic heart disease and its pathological magnitudes.
Assuntos
Apêndice Atrial , Doença da Artéria Coronariana , Animais , Arteríolas/anatomia & histologia , Capilares/anatomia & histologia , HumanosRESUMO
INTRODUCTION: Salivary gland neoplasms are not uncommon lesions that are seen in the head and neck region. The role of cell cycle regulators as well as that of oncogenes remains unexplored in the pathogenesis of these neoplasms. AIM: Present study was conducted to evaluate the expression of p27 in the three common salivary gland neoplasms. MATERIALS AND METHODS: A total of 34 cases (19 pleomorphic adenoma, 8 mucoepidermoid carcinoma and 7 adenoid cystic carcinoma) were included. The sections were subjected to p27 staining and rated for the expression. RESULTS: Of the total 52.6% of pleomorphic adenoma cases, 25% of mucoepidermoid carcinoma cases and only 14.2% of adenoid cystic carcinoma cases showed strong expression suggesting variable p27 expression in both malignant neoplasms. Normal salivary gland tissue was stained as a positive control for the evaluation. CONCLUSION: The results of the study suggest an important role for p27 in pathogenesis of mucoepidermoid carcinoma as well as adenoid cystic carcinoma while its role in pathogenesis of pleomorphic adenoma remains questionable keeping in view the strong expression of p27 in the same.
RESUMO
This paper reports the results of a comparative investigation of attitudes to suicide and suicidal persons in 5,572 university students from 12 countries. Participants filled out two scales measuring attitudes towards suicide and suicidal persons, a measure of psychological distress together with the questions about suicidal behavior. Results showed that the highest suicide acceptance scores were observed in Austrian, UK, Japanese and Saudi Arabian samples and the lowest scores were noted in Tunisian, Turkish, Iranian and Palestinian samples. While the highest social acceptance scores for a suicidal friend were noted in Turkish, US, Italian and Tunisian samples, the lowest scores were seen in Japanese, Saudi Arabian, Palestinian and Jordanian samples. Compared to participants with a suicidal past, those who were never suicidal displayed more internal barriers against suicidal behavior. Men were more accepting of suicide than women but women were more willing to help an imagined suicidal peer. Participants with accepting attitudes towards suicide but rejecting attitudes towards suicidal persons reported more suicidal behavior and psychological distress, and were more often from high suicide rate countries and samples than their counterparts. They are considered to be caught in a fatal trap in which most predominant feelings of suicidality such as hopelessness or helplessness are likely to occur. We conclude that in some societies such as Japan and Saudi Arabia it might be difficult for suicidal individuals to activate and make use of social support systems.