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1.
World J Microbiol Biotechnol ; 40(8): 251, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910228

RESUMO

Genetic diversity in Sclerotium rolfsii is useful for understanding its population structure, identifying different mycelial compatibility groups (MCGs), and developing targeted strategies for disease management in affected crops. In our study, a comprehensive genetic analysis was conducted on 50 isolates of S. rolfsii, collected from various geographic regions and host plants. Two specific genes, TEF1α and RPB2, were utilized to assess the genetic diversity and relationships among these isolates. Notably, out of 1225 pairings examined, only 154 exhibited a compatible reaction, while the majority displayed antagonistic reactions, resulting in the formation of a barrier zone. The isolates were grouped into 10 distinct MCGs. These MCGs were further characterized using genetic sequencing. TEF1α sequences distinguished the isolates into 17 distinct clusters, and RPB2 sequences classified them into 20 clusters. Some MCGs shared identical gene sequences within each gene, while others exhibited unique sequences. Intriguingly, when both TEF1α and RPB2 sequences were combined, all 10 MCGs were effectively differentiated, even those that appeared identical with single-gene analysis. This combined approach provided a comprehensive understanding of the genetic diversity and relationships among the S. rolfsii isolates, allowing for precise discrimination between different MCGs. The results shed light on the population structure and genetic variability within this plant pathogenic fungus, providing valuable insights for disease management and control strategies. This study highlights the significance of comprehending the varied virulence characteristics within S. rolfsii isolates, categorizing them into specific virulence groups based on disease severity index (DSI) values. The association with MCGs provides additional insights into the genetic underpinnings of virulence in this pathogen. Furthermore, the identification of geographical patterns in virulence implies the influence of region-specific factors, with potential implications for disease control and crop protection strategies.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [G. M. Sandeep] Last name [Kumar]. Author 2 Given name: [Praveen Kumar] Last name [Singh]. Also, kindly confirm the details in the metadata are correct.I confirm that the given names are accurate and presented in the correct sequence.


Assuntos
Basidiomycota , Variação Genética , Tipagem de Sequências Multilocus , Filogenia , Doenças das Plantas , Doenças das Plantas/microbiologia , Basidiomycota/genética , Basidiomycota/isolamento & purificação , Basidiomycota/classificação , Micélio/genética , Proteínas Fúngicas/genética , DNA Fúngico/genética , Produtos Agrícolas/microbiologia
2.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338849

RESUMO

Distal Sensory Peripheral Neuropathy (DSP) is a common complication in HIV-infected individuals, leading to chronic pain and reduced quality of life. Even with antiretroviral therapy (ART), DSP persists, often prompting the use of opioid analgesics, which can paradoxically worsen symptoms through opioid-induced microbial dysbiosis. This study employs the HIV Tg26 mouse model to investigate HIV-DSP development and assess gut microbiome changes in response to chronic morphine treatment and ART using 16S rRNA sequencing. Our results reveal that chronic morphine and ART exacerbate HIV-DSP in Tg26 mice, primarily through mechanical pain pathways. As the gut microbiome may be involved in chronic pain persistence, microbiome analysis indicated distinct bacterial community changes between WT and Tg26 mice as well as morphine- and ART-induced microbial changes in the Tg26 mice. This study reveals the Tg26 mouse model to be a relevant system that can help elucidate the pathogenic mechanisms of the opioid- and ART-induced exacerbation of HIV-associated pain. Our results shed light on the intricate interplay between HIV infection, ART, opioid use, and the gut microbiome in chronic pain development. They hold implications for understanding the mechanisms underlying HIV-associated pain and microbial dysbiosis, with potential for future research focused on prevention and treatment strategies.


Assuntos
Dor Crônica , Infecções por HIV , Doenças do Sistema Nervoso Periférico , Camundongos , Animais , Morfina/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Analgésicos Opioides/efeitos adversos , Disbiose , RNA Ribossômico 16S/genética , Qualidade de Vida
3.
J Contemp Dent Pract ; 24(9): 651-654, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38152937

RESUMO

AIM: The purpose of this study was to compare the three various techniques for measuring the alveolar ridge's dimensions prior to implant insertion. MATERIALS AND METHODS: For this study, a total of 36 participants were chosen. To prepare a surgical stent, a study model was created from an alginate impression. A first point (reference point) was marked on the crest of the ridge in relation to the adjacent teeth. Then, one point (point 1) and another point (point 2) were marked at distances of 3 and 6 mm, respectively, from the reference point. Based on the procedure for measuring the size of the alveolar ridge, the study was divided into the following groups. Group I: Cone-beam computed tomography (CBCT) measurement method; Group II: Ridge mapping measurement method; Group III: Direct caliper measurements method. Descriptive statistics were used to estimate the mean and standard deviation (SD). The Student's unpaired t-test was utilized for the statistical analysis. The 5% level of significance was used. RESULTS: There was no significant difference found between CBCT with ridge mapping and direct caliper measurements. However, on comparison of ridge mapping and direct caliper measurements technique, at point 1, the ridge mapping was 3.88 ± 0.12 and the direct caliper measurement was 3.62 ± 0.08. At point 2, the ridge mapping was 6.58 ± 0.06 and the direct caliper measurement was 6.32 ± 0.04. There was a statistically significant difference found between these two measurement methods. CONCLUSION: Within the limitation, the current study came to the conclusion that when CBCT and ridge mapping measurements were individually compared with the gold standard-the surgical open method, CBCT-demonstrated to be a highly specific and sensitive method for detecting the residual alveolar ridge width in the treatment planning of dental implants. CLINICAL SIGNIFICANCE: Evaluation of alveolar bone is necessary during treatment planning for dental implant placement. Using simply panoramic and/or periapical radiographs to evaluate the bone may not be sufficient because it only provides two-dimensional information regarding the implant locations. Therefore, for better implant placement, three-dimensional information of the implant site, such as CBCT and ridge mapping technique, should be assessed.


Assuntos
Processo Alveolar , Dente , Humanos , Processo Alveolar/diagnóstico por imagem , Implantação Dentária Endóssea , Tomografia Computadorizada de Feixe Cônico , Planejamento de Assistência ao Paciente
4.
Transpl Immunol ; 81: 101942, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37866671

RESUMO

BACKGROUND: Sepsis is a result of suppressed host immune response which leads to fatal multi-organ dysfunctionality. Low frequency of active monocytes or reduced expression of human leukocyte antigen (HLA)-DR on monocytes shows the suppressed immune response in sepsis patients. One of the well-studied markers in patients with sepsis is procalcitonin (PCT). The role of monocytic (m) HLA-DR expression has been monitored in sepsis and is being considered a marker of the severity of interim immuno-depression in these patients. The study describes the impact of HLA-DR expression on monocytes quantitatively using flow cytometry. METHODS: In this prospective study, we quantified monocytes and their HLA-DR expression in 20 patients of sepsis admitted to the Intensive Care Unit (ICU). Serum levels of PCT and interleukin (IL)-6 production were also measured in these patients, and the results were compared with those in healthy controls. RESULTS: Monocyte frequency calculated was higher in sepsis patients as compared to healthy controls, however, HLA-DR expressing monocytes were significantly reduced as was the mean fluorescence intensity (MFI) of HLA-DR. Contrastingly, IL-6 and PCT levels were significantly high in sepsis than controls. The results suggest that low HLA-DR expression, combined with PCT, is a better prognostic parameter in the early phase of sepsis. CONCLUSION: Poor recovery of mHLA-DR may serve as an early guide for clinicians to assess the prognosis of sepsis patients and consider immunomodulatory therapy in its management.


Assuntos
Anti-Infecciosos , Sepse , Humanos , Monócitos , Estudos Prospectivos , Estado Terminal , Antígenos HLA-DR/metabolismo , Anti-Infecciosos/metabolismo , Imunomodulação , Imunidade
5.
Heliyon ; 9(10): e20590, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37817995

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and declared a Public Health Emergency by the World Health Organization (WHO) on January 30, 2020. Albeit, unprecedented efforts have been made from the scientific community to understand the pathophysiology of COVID-19 disease, the host immune and inflammatory responses are not explored well in the Indian population. Continuous arrival of new variants fascinated the scientists to understand the host immune processes and to eradicate this deadly virus. The aim of this study was to see the helper and cellular host immune responses including memory and activated cell subsets of COVID-19 patients admitted to the intensive care unit (ICU) at different time intervals during the treatment. PBMCs separated from nine patients with SARS-CoV-2 infection were incubated with fluorescent conjugated antibodies and acquired on flow cytometer machine to analyze the T and B cell subsets. The results in COVID-19 patients versus healthy volunteers were as follows: elevated helper T cells (57.4% vs 44.9%); low cytotoxic T cells (42.8% vs 55.6%), and activated T (17.7% vs 21.2%) subsets. Both, TREG (40.15% vs 51.7%) and TH17 (13.2% vs 24.6%) responses were substantially decreased and high expression of TREG markers was observed in these patients compared with controls.

6.
J Pharm Bioallied Sci ; 15(Suppl 1): S447-S450, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37654402

RESUMO

Aim: The current study was conducted to evaluate the influence of frequently ingested beverages on the stability of suture materials. Materials and Methods: This research comprised of two kinds of chromic catgut, polyglactin 910 (4-0) absorbable suture materials. Every specimen was subjected to tying using a square surgeon's knot. Subsequent to pretensioning, 80 suture samples (40 of every material) were employed in this research. Every specimen was subjected to immersion in artificial saliva to replicate the oral atmosphere. Specimens were sunken in the acidic drink (Coca Cola) and tea for 10 min every day. Tensile strengths of the suture specimens were subjected to test at particular time periods: before immersion and 1, 7, and 14 days after immersion. Tensile strength evaluation of the suture specimens was performed employing the microtensile tester at a cross-head speed of 2.0 mm/60 s. Results: When subjected to exposure to acidic beverages, the tensile strength of chromic catgut suture before immersing was 25.14 ± 0.16, 25.02 ± 0.08 on the first day, 16.34 ± 0.23 on the seventh day, and 9.18 ± 0.28 on the fourteenth day. When the suture substance made contact with tea, the tensile strength before immersing was 24.48 ± 0.02, 24.14 ± 0.16 on the first day, 18.26 ± 0.11 on the seventh day, and 12.39 ± 0.14 on the fourteenth day. When subjected to exposure to acidic beverages, the tensile strength of polyglactin 910 sutures before immersing was 25.21 ± 0.02, 25.08 ± 0.01 on the first day, 18.12 ± 0.06 on the seventh day, and 10.06 ± 0.32 on the fourteenth day. When the suture substance made contact with tea, the tensile strength before immersing was 25.02 ± 0.14, 24.96 ± 0.04 on the first day, 20.48 ± 0.18 on the seventh day, and 14.10 ± 0.08 on the fourteenth day. The differences between the groups were statistically significant. Conclusion: In conclusion, polyglactin 910 exhibited a maintained strength superior than chromic catgut sutures subsequent to 14 days.

7.
J Contemp Dent Pract ; 24(7): 454-458, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37622622

RESUMO

AIM: The present study was designed to investigate the difference in the effectiveness of a 3 day postoperative course and a single perioperative dose of antibiotics on the incidence of postoperative infection in the management of maxillofacial trauma patients. MATERIALS AND METHODS: About 183 maxillofacial trauma patients requiring open reduction and internal fixation (ORIF) under general anesthesia were divided based on the type of fracture sustained, i.e., mandibular fractures, Le Fort fractures, and zygomaticomaxillary complex fractures. Patients from each fracture type were randomized into two groups, A and B. All patients were administered amoxicillin/clavulanate 1.2 grams intravenously 8 hours from the time of admission till the patient was taken up for surgery. Once the patients were taken up for surgery, a perioperative dose was administered. No antibiotics beyond this point were given to patients in Group A. Patients in Group B were administered the same antibiotic for 3 postoperative days additionally. Outcomes in terms of purulent discharge from the surgical site, an abscess or any other sign of infection, and wound dehiscence requiring reopening of the surgical site were considered. Patients were reviewed at 1 week, 2 weeks, 1 month, 2 months, and 3 months. RESULTS: No statistically significant difference was found between the two groups across all three fracture types in terms of postoperative outcomes. However, increased numbers of complications were noted in the patients treated with an intra-oral approach in each fracture type irrespective of group. All complications were managed with local measures. CONCLUSION: A single perioperative dose of antibiotics is effective in minimizing postoperative complications following ORIF of maxillofacial fractures and there is no significant benefit in prolonging the course of antibiotics postoperatively with the need for further studies to be conducted considering comminuted, complex fractures and old fractures. CLINICAL SIGNIFICANCE: In maxillofacial trauma, fractures frequently communicate with contaminated indigenous flora on the skin surface, oral cavities, or sinus cavities. Surgery is frequently performed using an approach across a contaminated area, even in closed fractures. Postoperative infections can be significantly decreased by using antibiotics in surgical procedures to treat facial fractures.


Assuntos
Fraturas Mandibulares , Fraturas Cranianas , Humanos , Estudos Prospectivos , Antibacterianos/uso terapêutico , Fraturas Cranianas/cirurgia , Fraturas Mandibulares/cirurgia , Combinação Amoxicilina e Clavulanato de Potássio , Complicações Pós-Operatórias/prevenção & controle
8.
Gut Microbes ; 15(2): 2246184, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37610102

RESUMO

Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of Parasuterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and depletion of Lactobacillus johnsonii. These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between Parasutterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria Lactobacillus johnsonii, metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community.


Assuntos
Microbioma Gastrointestinal , Transtornos Relacionados ao Uso de Opioides , Animais , Camundongos , Analgésicos Opioides , Disbiose/induzido quimicamente , Multiômica , Riboflavina , Derivados da Morfina , Lipídeos
9.
ACS Appl Bio Mater ; 6(9): 3778-3789, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37587788

RESUMO

It is an established fact that cancer is one of the most serious public health issues after coronary artery disease. Thus, exploring more effective and efficient therapeutic protocols over the traditional chemotherapeutic strategy is imperative to improving cancer survivorship and patient quality of life. In this respect, recent reports on molecularly engineered meso-substituted BODIPY have shown remarkable effects as a photoresponsive CO-releasing platform for the on-demand release of CO to treat cancer. Herein, we designed and synthesized two meso-substituted BODIPY photoresponsive CO-releasing molecules (photoCORMs). These BODIPY derivatives were tethered to a phenoxymethylpyridine moiety and oligoethylene glycol to maintain a hydrophilic-hydrophobic balance and improved cell permeability. The cell imaging experiments demonstrated that oligoethylene glycol containing photoCORM-1 efficiently internalized and preferentially localized at the mitochondria. To understand the mechanistic aspect of preferential localization into the mitochondria, live cell imaging was also carried out. Photorelease of CO was directly monitored by the inline IR spectroscopic technique. Finally, in vitro cytotoxicity and apoptosis assays on MDA-MB-231 cell lines clearly showed that photoCORM-1 induced apoptosis-mediated cell killing on account of photoreleased CO, which otherwise showed insignificant toxicity even at a very high concentration of ∼50 µM.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Apoptose , Glicóis , Mitocôndrias , Neoplasias/tratamento farmacológico
10.
Diagnostics (Basel) ; 13(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175029

RESUMO

Limited studies on candidemia in malignancy in the paediatric population from developing countries show a high incidence, high morbidity and a unique epidemiology as compared to developed nations. Our prospective observational study aimed to explore the prevalence of invasive candidiasis, especially candidemia, in febrile paediatric patients with lymphoreticular malignancy. A sample size of 49 children, with 100 recorded febrile episodes was studied. The relevance of candida colonization and mannan antigen detection as indicators of impending candidemia was evaluated. Genotypic identification of the yeast isolates was followed by sequence analysis using the NCBI-BLAST program, and the generation of the phylogenetic tree using MEGA 6.0 software. We observed a 5% prevalence of candidemia among febrile paediatric patients with lymphoreticular malignancy, predominantly caused by non-albicans candida. Colonization at multiple anatomical sites decreased from day 1 to day 8 of febrile episodes. Significant candida colonization (colonization index ≥0.5) was seen in a larger proportion of candidemia patients on day 1 and day 4 (p < 0.001) displaying a definite association between the two. The receiver operator characteristic (ROC) curve analysis for mannan antigen level revealed a cut-off of ≥104.667 pg/mL, suitable for predicting candidemia with a sensitivity of 100%, specificity of 92% and area under ROC value of 0.958 (95% CI: 0.915-1; p < 0.001). A phylogenetic tree with three population groups, clade 1, 2 and 3, consisting of Candida auris (1), Candida tropicalis (2) and Candida parapsilosis (2), respectively, was generated. The diagnosis of candidemia based on mannan antigen detection gives early results and has high negative predictive values. It can be combined with other biomarkers to increase sensitivity, specificity and positive predictive value.

11.
Phys Rev E ; 107(4-1): 044704, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37198864

RESUMO

For recent applications, liquid crystal-carbon nanotube based nanocomposite systems have been proven to be highly attractive. In this paper, we give a thorough analysis of a nanocomposite system made of both functionalized and nonfunctionalized multiwalled carbon nanotubes that are disseminated in a 4'-octyl-4-cyano-biphenyl liquid crystal medium. Thermodynamic study reveals a decrease in the nanocomposites' transition temperatures. In contrast to nonfunctionalized multiwalled carbon nanotube dispersed systems, the enthalpy of functionalized multiwalled carbon nanotube dispersed systems has increased. In comparison to the pure sample, the dispersed nanocomposites have a smaller optical band gap. A rise in the longitudinal component of permittivity and, consequently, the dielectric anisotropy of the dispersed nanocomposites has been observed by dielectric studies. When compared to the pure sample, the conductivity of both dispersed nanocomposite materials has increased by two orders of magnitude. For the system with dispersed functionalized multiwalled carbon nanotubes, the threshold voltage, splay elastic constant, and rotational viscosity all decreased. For the dispersed nanocomposite of nonfunctionalized multiwalled carbon nanotubes, the value of the threshold voltage is somewhat decreased but the rotational viscosity and splay elastic constant both are enhanced. These findings show the applicability of the liquid crystal nanocomposites for display and electro-optical systems with appropriate tuning of the parameters.

12.
Indian J Med Res ; 157(4): 250-258, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37102515

RESUMO

Background & objectives: There is a paucity of data regarding immunogenicity of recently introduced measles-rubella (MR) vaccine in Indian children, in which the first dose is administered below one year of age. This study was undertaken to assess the immunogenicity against rubella and measles 4-6 wk after one and two doses of MR vaccine administered under India's Universal Immunization Programme (UIP). Methods: In this longitudinal study, 100 consecutive healthy infants (9-12 months) of either gender attending the immunization clinic of a tertiary care government hospital affiliated to a medical college of Delhi for the first dose of routine MR vaccination were enrolled. MR vaccine (0.5 ml, subcutaneous) was administered to the enrolled participants (1st dose at 9-12 months and 2nd dose at 15-24 months). On each follow up (4-6 wk post-vaccination), 2 ml of venous blood sample was collected to estimate the antibody titres against measles and rubella using quantitative ELISA kits. Seroprotection (>10 IU/ml for measles and >10 WHO U/ml for rubella) and antibody titres were evaluated after each dose. Results: The seroprotection rate against rubella was 97.5 and 100 per cent and against measles was 88.7 per cent and 100 per cent 4-6 wk after the first and second doses, respectively. The mean (standard deviation) titres against rubella and measles increased significantly (P<0.001) after the second dose in comparison to the levels after the first dose by about 100 per cent and 20 per cent, respectively. Interpretation & conclusions: MR vaccine administered below one year of age under the UIP resulted in seroprotection against rubella and measles in a large majority of children. Furthermore, its second dose resulted in seroprotection of all children. The current MR vaccination strategy of two doses, out of which the first is to be given to infants below one year of age, appears robust and justifiable among Indian children.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Criança , Lactente , Humanos , Vacina contra Sarampo/uso terapêutico , Vacina contra Sarampo-Caxumba-Rubéola , Estudos Longitudinais , Anticorpos Antivirais , Rubéola (Sarampo Alemão)/prevenção & controle , Sarampo/prevenção & controle , Vacinação , Índia/epidemiologia
13.
Immunobiology ; 228(2): 152340, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36689824

RESUMO

The loss of balance between regulatory T (Treg) and T helper 17 (Th17) causes loss of tolerance against desmoglein (Dsg)-3 leading to pemphigus vulgaris (PV), an autoimmune bullous skin disorder associated with autoantibodies against Dsg-3. We aimed to elucidate the complex relationship of Th17 and Treg cells, their molecules, and the underlying mechanism in the development of PV disease. Using cytokine secretion assays, Th17 and Treg cells were sorted by FACS Aria-III within Dsg-3-responsive PBMC population and homogeneous T cell clones were generated in-vitro. Different cell surface molecules like CD25, GITR, CD122, CD152, CD45RO, IL-23R, STAT3, STAT5, CD127, HLA-DR, CCR4, CCR5, CCR6 and CCR7 were studied. The functional response of Th17 and Treg cells were elucidated by measuring the levels of various cytokines released by IL-10 and IL-17 T cells. The mRNA expression of transcription factors (FoxP3 and RORγt) was also analyzed. IL-17 secreting (Th17) cells with phenotype CD4+IL-17+ were greatly increased and IL-10 secreting (Treg) cells with phenotype CD4+IL-10+ were reduced in PV cases than healthy controls. The qPCR analysis showing high expression of retinoic acid receptor-related orphan receptor gamma (RORγt) mRNA in comparison to forkhead box P3 (FoxP3) mRNA confirmed the development of pro-inflammatory Th17 response in PV. Further, the cytokine profile of pro-inflammatory and anti-inflammatory cytokines suggested defective suppressive functions in Treg cells with high inflammatory response. Our findings indicate that autoantigen Dsg-3 specifically allows the proliferation of IL-17 secreting T cells though has a negative effect on IL-10 secreting T cells leading to dysregulation of immunity in PV patients. This antagonistic relationship between Dsg-3-specific Th17 and Treg cells may be critical for the onset and persistence of inflammation in PV cases.


Assuntos
Pênfigo , Linfócitos T Reguladores , Humanos , Interleucina-17/metabolismo , Interleucina-10/metabolismo , Pênfigo/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Leucócitos Mononucleares/metabolismo , Citocinas/metabolismo , Células Clonais/metabolismo , Fenótipo , Fatores de Transcrição Forkhead/metabolismo , RNA Mensageiro/metabolismo , Desmogleínas/metabolismo , Células Th17
14.
Br J Pharmacol ; 180(12): 1582-1596, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36585367

RESUMO

BACKGROUND AND PURPOSE: Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine-mediated gastric inflammation. EXPERIMENTAL APPROACH: Mice were implanted with 25 mg slow-release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ-free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole. KEY RESULTS: Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine-mediated gastric pathology was significantly attenuated in germ-free mice, and reconstitution of morphine gastric microbiome in germ-free mice resulted gastric inflammation. In addition, morphine-mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine-induced gastric dysbiosis and preventing inflammation. CONCLUSION AND IMPLICATIONS: This study attributes morphine-induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine-associated pathophysiology.


Assuntos
Disbiose , Receptor 2 Toll-Like , Camundongos , Animais , Disbiose/induzido quimicamente , Morfina/farmacologia , Inibidores da Bomba de Prótons/efeitos adversos , Omeprazol/farmacologia , Analgésicos Opioides/farmacologia , Inflamação/tratamento farmacológico
15.
Sci Total Environ ; 858(Pt 3): 160137, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36375556

RESUMO

During 2015-2018, eight black carbon (BC) monitoring sites were established in Nepal and Bhutan to fill a significant data gap regarding BC measurement in Central Himalaya. This manuscript analyzes and presents data from these eight stations and one additional station on the Tibetan plateau (TP). Complex topography, varied emission sources, and atmospheric transport pathways significantly impacted the BC concentrations across these stations, with annual mean concentrations varying from 36 ng m-3 to 45,737 ng m-3. Higher annual mean concentrations (5609 ± 4515 ng m-3) were recorded at low-altitude sites than in other locations, with seasonal concentrations highest in the winter (7316 ± 2541 ng m-3). In contrast, the annual mean concentrations were lowest at high-altitude sites (376 ± 448 ng m-3); the BC concentrations at these sites peaked during the pre-monsoon season (930 ± 685 ng m-3). Potential source contributions to the total observed BC were analyzed using the absorption angstrom exponent (AAE). AAE analysis showed the dominance of biomass burning sources (>50 %), except in Kathmandu. By combining our data with previously published literature, we put our measurements in perspective by presenting a comprehensive assessment of BC concentrations and their variability over the Hindu Kush Himalayan (HKH) region. The BC levels in all three geographic regions, high, mid, and low altitude significantly influenced by the persistent seasonal meteorology. However, the mid-altitude stations were substantially affected by valley dynamics and urbanization. The low-altitude stations experienced high BC concentrations during the winter and post-monsoon seasons. Concentration weighted trajectory (CWT) and frequency analyses revealed the dominance of long-range transported pollution during winter over HKH, from west to east. South Asian sources remained significant during the monsoon season. During pre- and post-monsoon, the local, regional, and long-distance pollution varied depending on the location of the receptor site.


Assuntos
Meteorologia , Urbanização , Nepal , Carbono
16.
Scand J Immunol ; 98(5): e13318, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38441343

RESUMO

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps. The study included 50 cases of CRSwNP and 50 healthy controls. Biopsies were subjected to KOH and culture for mycological investigation. We examined the changes in T helper (CD4+) and T cytotoxic (CD8+) in total T cells (CD3+) and expression of naive (CD45RA) and memory (CD45RO) cell markers in T cell subsets in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens in cases before and after treatment and in healthy controls by flow cytometry. Predominantly, A. flavus (86%) identified in nasal polyp biopsies of patients. An increased percentage of CD3+CD4+ T cells observed after A. flavus stimulation in patients when compared with healthy controls. The expression of CD4+CD45RA+ cells was significantly (P < .05) reduced in patients and increased CD4+CD45RO+ was observed upon stimulation with A. flavus in patients when compared with healthy control. Continuous exposure to inhaled fungal spores may induce aberrant immune responses to A. flavus spores, causing an allergic immunological reaction with high CD4+T cell responses, resulting in an unfavourable outcome. Elevated CD4+CD45RO+ T cells may transform the pathogenic response and highlight the chances of A. flavus reactive T cells involvement in prompting inflammation in CRSwNP.


Assuntos
Hipersensibilidade , Pólipos Nasais , Rinossinusite , Humanos , Aspergillus flavus , Leucócitos Mononucleares , Subpopulações de Linfócitos T , Antígenos Comuns de Leucócito
17.
Pharmaceutics ; 14(9)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36145627

RESUMO

Despite the many advancements in the field of pain management, the use of intravenous opioids, such as morphine, in neonates is still a challenge for clinicians and researchers, as the available evidence concerning the long-term consequences of such an early exposure is limited. In particular, little is known concerning the long-term consequences of neonatal morphine exposure on the gut microbiome, which has been identified as a key modulator of health and diseases. Consequently, the purpose of this study was to investigate those long-term consequences of neonatal morphine on the gut microbiome. Newborn mice were exposed to either morphine (5 mg/kg/day) or saline for a duration of 7 ± 2 days. Fecal samples were collected during adolescence and adulthood to longitudinally assess the gut microbiome. DNA extracted from the stool samples were sent out for 16s rRNA sequencing. During adolescence, neonatal morphine resulted in a significant increase of α-diversity and an overall decrease in the abundance of several commensal genera. During adulthood, ß-diversity revealed a significantly different microbial composition of the neonatally morphine-exposed mice than that of the controls. The results demonstrate that morphine exposure during this critical developmental period resulted in long-lasting changes, particularly a reduction in several commensal bacteria. Thus, an adjunct therapeutic intervention with probiotics could potentially be used along with opioids to manage pain while attenuating the long-term co-morbidities of neonatal morphine later in life.

18.
Plants (Basel) ; 11(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36015442

RESUMO

Marker-assisted selection (MAS) has been widely used in the last few decades in plant breeding programs for the mapping and introgression of genes for economically important traits, which has enabled the development of a number of superior cultivars in different crops. In sugarcane, which is the most important source for sugar and bioethanol, marker development work was initiated long ago; however, marker-assisted breeding in sugarcane has been lagging, mainly due to its large complex genome, high levels of polyploidy and heterozygosity, varied number of chromosomes, and use of low/medium-density markers. Genomic selection (GS) is a proven technology in animal breeding and has recently been incorporated in plant breeding programs. GS is a potential tool for the rapid selection of superior genotypes and accelerating breeding cycle. However, its full potential could be realized by an integrated approach combining high-throughput phenotyping, genotyping, machine learning, and speed breeding with genomic selection. For better understanding of GS integration, we comprehensively discuss the concept of genetic gain through the breeder's equation, GS methodology, prediction models, current status of GS in sugarcane, challenges of prediction accuracy, challenges of GS in sugarcane, integrated GS, high-throughput phenotyping (HTP), high-throughput genotyping (HTG), machine learning, and speed breeding followed by its prospective applications in sugarcane improvement.

19.
J Maxillofac Oral Surg ; 21(1): 184-190, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35400921

RESUMO

Objectives: To compare and evaluate the modified tragus edge approach (MTEA) with retromandibular approach for surgical access to mid-level or low-level mandibular condylar fractures. Materials and Methods: This study comprised of 22 patients with mid-level or low-level condylar fracture. Patients with clinical and radiological evidence of mid-level or low-level condylar fracture are included only in this study. Patients were randomly divided into two groups: group A includes 11 patients, in which modified tragus edge approach was used, and group B includes 11 patients treated with retromandibular approach. Patients were evaluated clinically after first week, second week, fourth week, third month, and sixth month radiographically. Results: The mean age of the study subjects in group A was 32.45 ± 8.98 years, while in group B, the mean age was 26.91 ± 5.79 years. Post-operatively, no significant difference was seen in relation to pain, occlusal relationship, mouth opening, and deviation of jaw during opening and closing movements. In terms of post-operative complication, only significant difference found between two groups is post-operative scar visibility, which is higher in retromandibular incision group as compared to MTEA. Conclusion: Thus, we can conclude that MTEA provides ease of operation as a good exposure of mandibular mid- or low-level condylar fracture as retromandibular approach but with less visibility of post-operative scar as compared to retromandibular approach.

20.
Cells ; 11(6)2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35326441

RESUMO

Tumor-derived cachectic factors such as proinflammatory cytokines and neuromodulators not only affect skeletal muscle but also affect other organs, including the heart, in the form of cardiac muscle atrophy, fibrosis, and eventual cardiac dysfunction, resulting in poor quality of life and reduced survival. This article reviews the holistic approaches of existing diagnostic, pathophysiological, and multimodal therapeutic interventions targeting the molecular mechanisms that are responsible for cancer-induced cardiac cachexia. The major drivers of cardiac muscle wasting in cancer patients are autophagy activation by the cytokine-NFkB, TGF ß-SMAD3, and angiotensin II-SOCE-STIM-Ca2+ pathways. A lack of diagnostic markers and standard treatment protocols hinder the early diagnosis of cardiac dysfunction and the initiation of preventive measures. However, some novel therapeutic strategies, including the use of Withaferin A, have shown promising results in experimental models, but Withaferin A's effectiveness in human remains to be verified. The combined efforts of cardiologists and oncologists would help to identify cost effective and feasible solutions to restore cardiac function and to increase the survival potential of cancer patients.


Assuntos
Cardiopatias , Neoplasias , Caquexia/etiologia , Caquexia/metabolismo , Citocinas , Cardiopatias/metabolismo , Humanos , Atrofia Muscular/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Qualidade de Vida
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