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1.
Cureus ; 16(6): e61697, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975478

RESUMO

In the early 20th century, numerous in-vitro studies, animal studies, epidemiological studies, and human trials have attempted to demonstrate the interrelationship between pregnancy outcomes and maternal periodontal disease. This review aims to shed light on the unexplored connections between pregnancy outcomes and maternal periodontal diseases. A literature search was conducted using electronic databases such as PubMed, Scopus, Google Scholar, Web of Science, and Embase. Our research focuses on the role of epigenetics, maternal vitamin D status, stress levels, genetic factors, innate immunity, pattern recognition receptors, and any potential paternal influence, and their possible connections to maternal periodontal disease. Although the precise etiologies and pathogenic mechanisms of the adverse pregnancy outcomes remain obscure, substantial affirmation of the inter-relationship between maternal periodontal diseases and adverse pregnancy outcomes may prove to be of public health relevance as periodontitis can certainly be prevented and treated. Maternal periodontal disease may augment the probability of jeopardizing maternal health causing adverse effects on the pregnancy and neonatal morbidity. Hence, emphasis should be placed on an early diagnosis and management of periodontal diseases. Routine oral health evaluation during prenatal care should be encouraged to combat complications. Ensuing endeavors should be undertaken to help find plausible mechanisms keeping in view the future research domains and new pathways.

2.
ACS Appl Bio Mater ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943669

RESUMO

In this study, we design and simulate a metal implanted dielectrically modulated tunneling field-effect transistor (MI-DMTFET). In the ambipolar conduction state, the proposed structure works as an efficient sensor for the detection of a wide range of biomolecules. A metal strip (MS) is implanted above the drain-channel junction in the gate dielectric to improve the alignment of band gaps. Therefore, with the help of implanted metal work function engineering, the tunneling barrier gets lowered, which in turn increases the ambipolar current. An optimum metal-strip implant work function of 4.85 eV and a length of 1.5 nm have resulted in significantly improved performance of the proposed device. It has been observed that when the biomolecules with varying dielectric constants and charge densities are captured in the nanogap cavity, the ambipolar current of the biosensor changes, resulting in the detection of the biomolecules. Quantitative and comprehensive analyses of device parameters such as surface potential, electric field, band-to-band tunneling, subthreshold slope, and ION/IOFF ratio analysis have been performed. Rigorous comparative analyses of key performance-measuring parameters have been performed with a conventional sensor device. It has been found that the proposed device offers maximum sensitivity of 1220 under an ambipolar state at k = 12.

3.
Cureus ; 16(4): e58288, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38752055

RESUMO

Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both males and females are affected, although it predominantly affects females in their fifth and sixth decades of life. Approximately 1.4 to 3.7% of PV cases occur in the pediatric population (≤18 years of age), and may be classified into childhood/pediatric PV, which affects individuals under 12 years old, and juvenile/adolescent PV, affecting those between 12 and 18 years old. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. A systematic literature search was conducted on MEDLINE/PubMed, Web of Science, EMBASE, SCOPUS, and Cochrane Library databases to evaluate the efficacy of rituximab (RTX) in childhood and juvenile PV patients. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed to assess the risk of bias in case reports and series, while the Cochrane ROBINS-I tool was utilized for evaluating observational studies or non-randomized intervention studies. A total of 18 studies encompassing 46 juvenile or childhood PV patients in the pediatric and adolescent age groups were included for qualitative synthesis. The studies included nine case reports, two case series, five retrospective studies, one prospective study, and one open-label pilot study. Almost all cases of childhood and juvenile PV achieved either complete or partial remission after undergoing RTX treatment during the final follow-up periods. Furthermore, most cases reported no relapse, and only minor adverse events were noted in the RTX treatment group. Despite its potential benefits, the utilization of RTX in pediatric patients raises concerns due to the scarcity of evidence and the absence of controlled studies specific to this age group. Further exploration is necessary to establish a standardized treatment regimen for RTX in pediatric PV, which involves identifying the optimal dosage, frequency, treatment cycle duration, and maintenance therapy duration.

4.
Fitoterapia ; 175: 105927, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548028

RESUMO

STAT3 is a crucial member within a family of seven essential transcription factors. Elevated STAT3 levels have been identified in various cancer types, notably in breast cancer (BC). Consequently, inhibiting STAT3 is recognized as a promising and effective strategy for therapeutic intervention against breast cancer. We herein synthesize a library of isoxazole (PAIs) from piperic acid [2E, 4E)-5-(2H-1,3-Benzodioxol-5-yl) penta-2,4-dienoic acid] on treatment with propargyl bromide followed by oxime under prescribed reaction conditions. Piperic acid was obtained by hydrolysis of piperine extracted from Piper nigrum. First, we checked the binding potential of isoxazole derivatives with breast cancer target proteins by network pharmacology, molecular docking, molecular dynamic (MD) simulation and cytotoxicity analysis as potential anti-breast cancer (BC) agents. The multi-source databases were used to identify possible targets for isoxazole derivatives. A network of protein-protein interactions (PPIs) was generated by obtaining 877 target genes that overlapped gene symbols associated with isoxazole derivatives and BC. Molecular docking and MD modelling demonstrated a strong affinity between isoxazole derivatives and essential target genes. Further, the cell viability studies of isoxazole derivatives on the human breast carcinoma cell lines showed toxicity in all breast cancer cell lines. In summary, our study indicated that the isoxazole derivative showed the significant anticancer activity. The results highlight the prospective utility of isoxazole derivatives as new drug candidates for anticancer chemotherapy, suggesting route for the continued exploration and development of drugs suitable for clinical applications.


Assuntos
Ácidos Graxos Insaturados , Isoxazóis , Simulação de Acoplamento Molecular , Fator de Transcrição STAT3 , Neoplasias de Mama Triplo Negativas , Humanos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Isoxazóis/farmacologia , Isoxazóis/química , Linhagem Celular Tumoral , Estrutura Molecular , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos Insaturados/isolamento & purificação , Ácidos Graxos Insaturados/química , Farmacologia em Rede , Simulação de Dinâmica Molecular , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação
5.
Cureus ; 16(1): e53115, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38283781

RESUMO

BACKGROUND: Gallbladder perforation and gallstone leakage are frequent complications following laparoscopic cholecystectomy (LC). Failure to remove gallstones may result in several issues that manifest immediately or years later. The goal of this study was to evaluate the attitudes of surgeons and the procedures used by them to deal with gallstone spillage during LC. METHODS: A cross-sectional design was followed. Surgeons in nine healthcare facilities in the Qassim region of Saudi Arabia were approached through non-probability convivence sampling and the survey was distributed in each of the general surgery divisions. The study included general surgeons who currently performed LC and incomplete responses and interns were excluded. A self-administered questionnaire was developed with 18 questions regarding demographics, center, and designation at the hospital, surgeons' experience of LC, and exposure to gallstone spillage. Furthermore, items regarding knowledge, attitude, and self-reported practices related to gallstone spillage such as incidence, complications, and intervention taken to prevent gallstone spillage were also included. The level of significance was set at P <0.05. RESULTS: There were 82 participants of both genders, including consultants, specialists, and residents. While only 23 (28%) participants had actually observed patients with complications from spilled stones, 46 (56.1%) participants were aware of this possibility, 53 (64.6%) deemed it inappropriate to bring up gallstone spillage when securing consent for LC, and 67 (81.7%) believed that such an incident needed to be documented in the operation notes. Only 11 (13.4%) thought that the complications arising out of the unretrieved gallstones should fall under the legal purview of the operative surgeon. There were very few complications of spilled gallstones that the participants were aware of, and none of them anticipated problems to arise more than three years after LC. CONCLUSIONS: Awareness of the risks associated with gallstone spillage during LC needs to be raised, and it is imperative to standardize the practices related to their management.

6.
bioRxiv ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38168185

RESUMO

The current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RARγ's ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RARγ complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RARγ complex. RARγ significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RARγ expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RARγ functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RARγ were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RARγ, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.

7.
Front Immunol ; 14: 1265038, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942326

RESUMO

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterise differential gene expression in γδ T cells - a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10-12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the M. bovis-infected compared to the control groups for the WC1.1+ γδ T cell compartment (absolute log2 FC ≥ 1.5 and FDR P adj. ≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM, and GZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, γδ T cells have important inflammatory and regulatory functions in cattle, and we provide evidence for preferential differential activation of the WC1.1+ specific subset in cattle naturally infected with M. bovis.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Animais , Bovinos , Humanos , Subpopulações de Linfócitos T , Receptores de Antígenos de Linfócitos T gama-delta , Expressão Gênica
8.
bioRxiv ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38014010

RESUMO

We have dissected the role of Estrogen receptor beta (ERß) in prostate cancer (PCa) with a novel ERß ligand, OSU-ERb-12. Drug screens revealed additive interactions between OSU-ERB-12 and either epigenetic inhibitors or the androgen receptor antagonist, Enzalutamide (Enza). Clonogenic and cell biolody studies supported the potent additive effects of OSU-ERB-12 (100nM) and Enza (1µM). The cooperative behavior was in PCa cell lines treated with either OSU-ERB-12 plus Enza or combinations involving 17ß-estradiol (E2). OSU-ERb-12 plus Enza uniquely impacted the transcriptiome, accessible chromatin, and the AR, MYC and H3K27ac cistromes. This included skewed transcriptional responses including suppression of the androgen and MYC transcriptomes, and repressed MYC protein. OSU-ERb-12 plus Enza uniquely impacted chromatin accessibility at approximately 3000 nucleosome-free sites, enriched at enhancers, enriched for basic Helix-Loop-Helix motifs. CUT&RUN experiments revealed combination treatment targeting of MYC, AR, and H3K27ac again shaping enhancer accessibility. Specifically, it repressed MYC interactions at enhancer regions enriched for bHLH motifs, and overlapped with publicly-available bHLH cistromes. Finally, cistrome-transcriptome analyses identified ~200 genes that distinguished advanced PCa tumors in the SU2C cohort with high androgen and low neuroendocrine scores.

9.
Cureus ; 15(7): e41635, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37565114

RESUMO

Introduction The antiseptic skin preparation, bladder irrigation, corner-saving vascular anastomosis, DJ stenting, and extravesical ureteroneocystostomy (ABCDE) approach encompasses a range of modifications applied during different stages of the surgical procedure in renal transplantation. These modifications include the following: A, antiseptic skin preparation sequentially with cetrimide 3.35%, chlorhexidine scrub 4%, spirit, and povidone-iodine 10%; B, bladder irrigation with amikacin and betadine solution; C, corner-saving end-to-side vascular anastomosis; D, DJ stenting with early postoperative removal within three weeks; and E, extravesical ureteroneocystostomy using our institute's modified Lich-Gregoir technique. Methods This prospective observational study was conducted at our institution between March 2021 and May 2023. Data were collected from the patients' medical records and analyzed using Statistical Package for the Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY, USA). Statistical tests, including t-test, Mann-Whitney test, chi-square test, and Fisher's exact test, were used for analysis. The study assessed various recipient, donor, intraoperative, and post-transplant factors, as well as surgical complications and stent-related factors. Results Out of 72 renal transplantations, 12 (16.6%) had the following surgical complications: urinary (n = 4; 5.5%), wound-related (n = 3; 4.1%), and lymphocele (n = 5; 6.9%). The most common complications were lymphocele (n = 5; 6.9%) and urinary leak (n = 4; 5.5%). Surgical complications were more common in male recipients (91.6% versus 8.3%), as well as in recipients with longer dialysis duration (24 ± 17 versus 11.0 ± 7 months) and had extended hospitalization time (16.4 ± 8.6 versus 8.0 ± 2.9 days) (p < 0.05). Wound infection correlated with longer surgeries (>300 minutes) and other complications. Lymphocele patients had higher drain output (>500 mL) on day 1 and longer hospital stays (>15 days). Urinary tract infections (UTIs) were linked to dialysis duration (>24 months), diabetes, and longer indwelling times of DJ stents and urinary catheters. Early DJ stent removal (<3 weeks) reduced UTI incidence and symptoms (p < 0.05). All complications were categorized as minor (3a or less), according to the Clavien-Dindo classification. Conclusion The modified ABCDE surgical approach in renal transplantation decreased the complications, showing favorable outcomes compared to those in the literature.

11.
Gene ; 878: 147583, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37353040

RESUMO

BACKGROUND: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. METHOD: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. RESULTS: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. CONCLUSION: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , RNA Mensageiro/genética , Neoplasias da Bexiga Urinária/genética
12.
J Family Med Prim Care ; 12(2): 403-405, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37091000

RESUMO

A 70-year-old male with a known case of beta-thalassemia trait and was on yearly follow-up was found to have a hemoglobin of 14.8 g/dL, hematocrit of 47.7%, and RBC count of 6.0 × 1012/L. Total leukocyte count (TLC) was 5 × 109/L and platelet count was 4 × 109/L. Secondary causes of polycythemia were ruled out (e.g., renal or cardiac disease and smoking). He did not have symptoms of hyperviscosity syndrome. The abdominal ultrasound showed no abnormalities. On further investigation, a JAK-2 (Exon 14) mutation was detected in this patient confirming the diagnosis of polycythemia vera (PV).

13.
Cancer Res Commun ; 3(4): 621-639, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37082578

RESUMO

African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function. Significance: Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.


Assuntos
Neoplasias da Próstata , Receptores de Calcitriol , Masculino , Humanos , Receptores de Calcitriol/genética , Transcriptoma/genética , Negro ou Afro-Americano/genética , Neoplasias da Próstata/genética , Cromatina/genética , Proteínas Cromossômicas não Histona/genética
14.
J Mycol Med ; 33(1): 101331, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36272379

RESUMO

Dermatophytosis is a common superficial fungal infection of the skin and its appendages caused by dermatophytes. Recent times have witnessed a dynamic evolution of dermatophytes driven by their ecology, reproduction, pathogenicity and host immune response, influenced by population migration and socioeconomic status. Dermatophytes establish infection following successful adherence of arthroconidia to the surface of keratinized tissues. The proteolytic enzymes released during adherence and invasion not only ascertain their survival but also allow the persistence of infection in the host. While the cutaneous immune surveillance mechanism, after antigen exposure and presentation, leads to activation of T lymphocytes and subsequent clonal expansion generating effector T cells that differentially polarize to a predominant Th17 response, the response fails to eliminate the pathogen despite the presence of high levels of IFN-γ. In chronic dermatophytosis, antigens are a constant source of stimulus promoting a dysregulated Th17 response causing inflammation. The host-derived iTreg response fails to counterbalance the inflammation and instead polarizes to Th17 lineage, aggravating the chronicity of the infection. Increasing antifungal resistance and recalcitrant dermatophytosis has impeded the overall clinical remission. Human genetic research has the potential to generate knowledge to explore new therapeutic targets. The review focuses on understanding specific virulence factors involved in pathogenesis and defining the role of dysregulated host immune response against chronic dermatophytic infections for future management strategies.


Assuntos
Arthrodermataceae , Dermatomicoses , Tinha , Humanos , Arthrodermataceae/genética , Dermatomicoses/microbiologia , Interações Hospedeiro-Patógeno , Tinha/microbiologia , Inflamação , Trichophyton/genética
15.
Cureus ; 14(11): e31884, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36579283

RESUMO

Tyrosine kinase inhibitors (TKIs) remain the mainstay of treatment for those with chronic myeloid leukemia (CML); nonetheless, there is concern over the possibility of additional cancers as a result of TKI use. There are not many cases in the literature where tyrosine kinase treatment caused a patient to develop secondary lymphoma. Herein we present a 49-year-old male diagnosed with CML in 2014, on Imatinib for six years with a major molecular response, who presented with generalized lymphadenopathy in July 2020. The complete evaluation was done, and histopathology and immunohistochemistry revealed follicular lymphoma. He responded well to six cycles of bendamustine and rituximab treatment (BR). It is critical for treating physicians to be aware of such occurrences, and patients on TKI must be closely monitored.

16.
Cureus ; 14(10): e29890, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36348826

RESUMO

OBJECTIVE: The purpose of this study was to assess the serum levels of cytokines produced by the Th1 (IFN-γ, IL-12), Th2 (IL-4), Th17 (IL-6, IL-17A, IL-23), and Treg (IL-10 and TGF-ß) pathways in individuals with active pemphigus vulgaris (PV) and to determine whether these levels were correlated with the severity of the disease condition. PATIENTS AND METHODS: This study was conducted with 90 individuals, of which 50 were PV patients and 40 healthy individuals (age and gender-matched) as controls. Serum samples were collected and tested for cytokine levels by ELISA (enzyme-linked immunosorbent assay). The cytokine levels in the serum of PV patients and healthy controls were compared statistically using the Mann-Whitney test for nonparametric samples. The strength of the association between the variables was evaluated using the Spearman correlation test. RESULTS: The mean serum levels of IFN- γ (p < 0.001), IL-6 (p < 0.001), IL-10 (p < 0.001), IL-12 (p < 0.05), and IL-17 (p < 0.001) were significantly higher and TGF-ß were significantly low in the PV patients than those observed in the control group. The mean concentration of serum IL-4 in patients with PV did not differ from those in the control group. CONCLUSIONS: In active PV, the Th1 and Th17 pathways are involved in the development and progression of the disease, whereas the Th2 pathway is blocked. Both of these pathways play a significant role in the disease. It is possible that the Treg pathway acts as an antagonist to the Th1 and Th17 pathways, which would cause the disease to become more localised. This study lays the foundation for a better understanding of the aetiology of PV and implies that cytokines could be used as potential therapeutic targets and disease activity biomarkers.

17.
Cureus ; 14(10): e30468, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36407189

RESUMO

Background Hemorrhage after trauma is the second leading cause of death in patients in the prehospital environment, and intervention by bystanders before the arrival of professional rescuers has the potential to save lives in such circumstances. No studies have been conducted in Saudi Arabia till date to assess the knowledge and awareness of bleeding control by bystanders. Hence, this study was conducted with an aim to assess the level of awareness, attitude, and willingness toward bleeding control by bystanders in Riyadh city, the capital of Kingdom of Saudi Arabia (KSA). Methodology This is an observational cross-sectional survey design that was conducted from July 2022 to August 2022 using an electronic questionnaire targeting populations who live in Riyadh city. MS Excel 2022 was used for data entry and coding, while SPSS Version 26 (IBM Corp., Armonk, NY) was used for data analysis. Results In this study, 585 adults from Riyadh city were recruited. Among the participants, 62.9% of them were between 16 and 26 years of age; 55.4% were males and 90.3% were Saudi Arabian citizens. Of the participants, 76.1% reported that they did not have any experience in participation in bleeding control related activity. Fear of causing more harm to the patients by attempting bleeding control was expressed by 65.1%. In general, 40.2% of the participants have adequate knowledge considering controlling of bleeding in an emergency setting. Higher level of education and having a previous first aid training were associated with better knowledge significantly (p=0.001 and 0.012, respectively). Conclusion There is a great need to improve the level of awareness about the role of bystanders in bleeding control and to design community-level activities to popularize this important life-saving skill.

18.
RSC Adv ; 12(42): 27179-27188, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36276049

RESUMO

In this work, we propose and simulate an ultrasensitive, label-free, and charge/dielectric modulated Si:HfO2 ferroelectric junctionless tunnel field effect transistor (FE-JL-TFET) based biosensor. The proposed sensing device employs a dual inverted-T cavity and uses ferroelectric gate stacking of Si-doped HfO2, a key enabler of negative capacitance (NC) behavior. The two cavities are carved in gate-source underlap regions by a sacrificial etching technique to sense biomolecules such as streptavidin (2.1), bacteriophage T7 (6.3) and gelatin (12). Two dimensional (2D) calibrated simulations have been performed and the impact of various device parameters, including cavity length and height, on various performance measuring parameters has been studied. It has been observed that the biosensor exhibits better sensitivities for both neutral and charged biomolecules. The maximum values of the I ON/I OFF sensitivity for the neutral, positively charged and negatively charged biomolecules are as high as 3.77 × 109, 5.85 × 109, and 1.72 × 1010, respectively. It has been observed that optimizing the cavity length and height can significantly improve the sensing capability of the proposed device. The comparative analysis of the proposed biosensor and other state of the art biosensors shows a significant improvement in the sensitivity (101 to 106 times) in the proposed biosensor. The detrimental effect of interface trapped charges on the biosensor performance is also analyzed in detail.

19.
Sci Rep ; 12(1): 16923, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209294

RESUMO

In the present study, chitosan (CH) based biodegradable films were developed enriched with thyme essential oil (TEO) incorporated with different additives including zinc oxide (ZnO), polyethylene glycol (PEG), nano clay (NC), and calcium chloride (CaCl2) and characterize the postharvest quality of 'collard greens' during refrigerated storage. The results indicated that the incorporation of ZnO/PEG/NC/CaCl2 in CH-based films significantly decreased water vapor transmission rate, increased tensile strength, and were water soluble and biodegradable in nature. Moreover, CH-TEO based films incorporated with ZnO/PEG/NC/CaCl2 were significantly effective in reducing physiological weight loss, retained total soluble solids, titratable acidity, and preserved chlorophyll contents as well as showed lesser a* values, suppressed microbial growth, and preserving appearance/sensory quality of collard greens for 24 days than LDPE and other biodegradable films. Our results suggest that CH-based films enriched with TEO and additives such as ZnO/CaCl2/NC/PEG are an ecological, environmental friendly, and effective alternative approach to retain shelf life of collard greens during refrigerated storage.


Assuntos
Brassica , Quitosana , Óleos Voláteis , Thymus (Planta) , Óxido de Zinco , Cloreto de Cálcio , Clorofila , Argila , Escherichia coli , Embalagem de Alimentos/métodos , Polietileno , Polietilenoglicóis , Vapor
20.
Adv Exp Med Biol ; 1390: 227-239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107322

RESUMO

Alterations in transcriptional programs are a fundamental feature of prostate (PCa) and breast cancer (BrCa), and frequently target the actions of the principal steroidal nuclear receptors (NRs), namely the androgen receptor (AR) and the estrogen receptor alpha (ERα), respectively. Indeed, the functions of AR and ERα are central to both prostate and mammary gland biology. The genomic interactions of these NRs become highly distorted in part by changing how they functionally interact with a cohort of non-steroidal Type II NRs, which are by contrast relatively understudied compared to their steroidal cousins. For example, the AR cistrome overlaps with cistromes of different Type II NRs, which suggests a high potential for integrated NR functions to tailor transcriptional signals. Over recent years the cistromes of these Type II NRs, including HNF4s, RARs, PPARs and VDR, have been studied in PCa and BrCa revealing convergence and functional consequences, and are reviewed in the current chapter.


Assuntos
Neoplasias da Mama , Próstata , Neoplasias da Mama/genética , Receptor alfa de Estrogênio , Genômica , Humanos , Masculino , Receptores Ativados por Proliferador de Peroxissomo , Receptores Androgênicos/genética
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