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1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 40: e20240004, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902996

RESUMO

The human immune system plays a pivotal role in protecting the body against pathogens, maintaining homeostasis, and preventing disease. Immunomodulation, the process of regulating immune responses, is crucial for optimal health. In recent years, there has been growing interest in natural remedies for immune system modulation, driven by the recognition of their potential efficacy and safety profiles. This project aims to investigate the immunomodulatory effects of drumstick leaves tablets, derived from Moringa oleifera, a plant known for its rich nutritional and medicinal properties. The study will explore the potential of drumstick leaves tablets to modulate immune responses through in vitro and in vivo experiments. Through comprehensive analysis of the immunomodulatory properties of drumstick leaves tablets, this project aims to contribute to our understanding of natural remedies for immune system modulation. The findings could have significant implications for the development of novel therapeutic interventions aimed at enhancing immune function and improving human health.


Assuntos
Agentes de Imunomodulação , Moringa oleifera , Folhas de Planta , Comprimidos , Moringa oleifera/química , Folhas de Planta/química , Agentes de Imunomodulação/farmacologia , Animais , Fatores Imunológicos/farmacologia , Camundongos , Humanos , Medicamentos de Ervas Chinesas/farmacologia
2.
J Am Nutr Assoc ; : 1-8, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935369

RESUMO

OBJECTIVE: Our aim in this study is, does 29-day regular consumption of Pleurotus ostreatus water extract by volunteer individuals who meet the study criteria have an effect on blood and cytokine values? METHOD: In accordance with the purpose of the study, volunteers were asked to consume 100 ml of the extract every morning for 29 days. Three tubes of blood samples were taken from the volunteers on the 15th and 29th days of the study. Biochemical and hematological analysis of the blood samples were performed and immunomodulatory effects through cytokines were examined. The values obtained from 3 tubes of blood obtained from volunteers before the use of mushroom extract were used as control. The chemical composition and ß-glucan content of 100 ml of mushroom water extract were also analyzed. RESULT: IL-4, IL-6, IL-10 and IL-13 could not be detected because the values were below the lowest standard value. TNF-α, IFN-γ and IL-1ß 15th and 29th day values decreased compared to the 1st day (control) values (p < 0.05). However, there was no significant difference observed between the 15th and 29th day. No abnormalities were observed in biochemical and hematological values. Also, the ß-glucan content of extract was found 38.12 mg/100 ml. CONCLUSION: The frequency range of kidney and liver function test results confirmed that P. osreatus is a reliable food source. Considering the cytokine values these results indicate that P. ostreatus water extract has an anti-inflammatory effect. As no significant difference was observed in 29 days of use, it is thought that 15 days of daily consumption of the extract may be sufficient for the anti-inflammatory effect to occur. However, a large number of qualified clinical trials are needed to support the issue.

3.
Vet Sci ; 11(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38922001

RESUMO

The objective of this study was to investigate the therapeutic effects of inactivated Propionibacterium acnes and lipopolysaccharide derived from Escherichia coli cells in cats affected by feline panleukopenia virus (FPV). A retrospective study of 80 FPV-positive cats was divided into two groups: a treatment group receiving inactivated Propionibacterium acnes and lipopolysaccharide derived from Escherichia coli cells along with supportive treatment and a no-treatment group receiving only supportive treatment. There was no significant difference in the total white blood cell counts between the two groups. However, the total white blood cell counts of both groups were low on day 0 and increased significantly on days 3 and 6 of treatment. Additionally, the white blood cell counts in the treatment group significantly increased during days 3 to 6 compared with those of the no-treatment group (p < 0.01). The mortality rate was not significantly different between the two groups. In a prospective study, the serum and fecal immunoglobulin A (IgA) levels were measured in both groups. There were no significant differences in IgA levels between the two groups in either the serum or feces.

4.
Cureus ; 16(5): e59840, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38854354

RESUMO

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disorder characterized by recurrent episodes of demyelination affecting the central nervous system. The following case report showcases a thorough analysis of a 21-year-old female patient presenting with MOGAD, outlining her clinical presentation, diagnostic workup, treatment protocol, and long-term management outcomes. Through a multidisciplinary approach, we aim to augment the understanding of this complex neurological entity and steer optimal therapeutic interventions.

5.
ACG Case Rep J ; 11(6): e01368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883582

RESUMO

Treatment options for patients with inflammatory bowel disease are constantly evolving; however, medication-refractory disease remains an issue. Pediatric case series show the potential benefit of sirolimus therapy in refractory Crohn's disease (CD); however, limited data exist in adult patients. As such, we retrospectively identified and report clinical outcomes for 4 patients prescribed sirolimus for treatment of refractory CD. Despite a median sirolimus therapy duration of 524 days and some therapeutic benefits, all patients discontinued therapy due to adverse effects. Our findings suggest that while sirolimus may have clinical utility, its role may be limited by treatment-derived adverse effects.

6.
Dig Dis Sci ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877332

RESUMO

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy. METHODS: We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation. RESULTS: We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506 ng/mL (interquartile range (IQR) [416-750]) to 76.5 ng/mL (IQR [25.8-232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4 µg/mL (IQR [0.4-0.48]) to 8.25 µg/mL (IQR [3.7-9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72-94%], 6.7-fold increased IFX trough (95% CI = 2.4-18.7), and 76% clinical remission rescue rate (95% CI = 59-93%). CONCLUSIONS: These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD.

7.
J Infect Dis ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38942608

RESUMO

Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.

8.
Cureus ; 16(4): e58417, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38756289

RESUMO

Keytruda (pembrolizumab) is an immunomodulator that prevents the interaction between programmed cell death protein (PD-1) and programmed death ligand (PD-L1/2) on immune cells and tumour cells, thereby preventing T cell dysfunction. At times, mounting a strong immune response against tumour cells may not spare normal cells, leading to a variety of multisystemic adverse effects. With this, we present a case of a 64-year-old male who developed acute pancreatitis after completing eight cycles of Keytruda for castrate-resistant metastatic prostate cancer for six months, after all other causes of pancreatitis were excluded.

9.
Pharm Biol ; 62(1): 367-393, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38745507

RESUMO

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.


Assuntos
Neoplasias , Oryza , Xilanos , Xilanos/farmacologia , Humanos , Animais , Neoplasias/tratamento farmacológico , Produtos Biológicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Antineoplásicos/farmacologia
10.
Cureus ; 16(4): e58913, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38800281

RESUMO

BACKGROUND: Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic formulation, IMMBO, comprising Mandoor Bhasma and 18 herbs has shown promising results in treating allergic rhinitis in clinical studies. OBJECTIVE: This discussed series of experimental studies were conducted to explore the immuno-modulatory potential of IMMBO. METHODOLOGY: A series of experimental studies were carried out in immunosuppressed rats to explore the immune-modulatory effects of IMMBO. RESULTS: IMMBO was effective in reinstating neutrophil activation, stimulating cellular and humoral immunity, and counteracting immunosuppression at the molecular level. The modulation of key signalling molecules, including tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1ß), extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), and nuclear factor-kappa B (NF-κb), showcased the formulation's multifaceted impact. Additionally, its ability to block histamine release suggests potential in controlling allergic states, positioning it as a promising therapeutic candidate for immune-related disorders. However, the precise mode of action remains elusive, warranting further in-depth pharmacological studies. CONCLUSION: This research substantiates the ancient Ayurvedic wisdom using modern scientific parameters, endorsing IMMBO's potential as an immune-modulatory agent.

11.
Front Cell Dev Biol ; 12: 1271684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655063

RESUMO

Macrophages, the predominant immune cells in the lungs, play a pivotal role in maintaining the delicate balance of the pulmonary immune microenvironment. However, in chronic inflammatory lung diseases and lung cancer, macrophage phenotypes undergo distinct transitions, with M1-predominant macrophages promoting inflammatory damage and M2-predominant macrophages fostering cancer progression. Exosomes, as critical mediators of intercellular signaling and substance exchange, participate in pathological reshaping of macrophages during development of pulmonary inflammatory diseases and lung cancer. Specifically, in inflammatory lung diseases, exosomes promote the pro-inflammatory phenotype of macrophages, suppress the anti-inflammatory phenotype, and subsequently, exosomes released by reshaped macrophages further exacerbate inflammatory damage. In cancer, exosomes promote pro-tumor tumor-associated macrophages (TAMs); inhibit anti-tumor TAMs; and exosomes released by TAMs further enhance tumor proliferation, metastasis, and resistance to chemotherapy. Simultaneously, exosomes exhibit a dual role, holding the potential to transmit immune-modulating molecules and load therapeutic agents and offering prospects for restoring immune dysregulation in macrophages during chronic inflammatory lung diseases and lung cancer. In chronic inflammatory lung diseases, this is manifested by exosomes reshaping anti-inflammatory macrophages, inhibiting pro-inflammatory macrophages, and alleviating inflammatory damage post-reshaping. In lung cancer, exosomes reshape anti-tumor macrophages, inhibit pro-tumor macrophages, and reshaped macrophages secrete exosomes that suppress lung cancer development. Looking ahead, efficient and targeted exosome-based therapies may emerge as a promising direction for treatment of pulmonary diseases.

12.
Arch Microbiol ; 206(5): 205, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573383

RESUMO

Honeybees are vital for global crop pollination, making indispensable contributions to agricultural productivity. However, these vital insects are currently facing escalating colony losses on a global scale, primarily attributed to parasitic and pathogenic attacks. The prevalent response to combat these infections may involve the use of antibiotics. Nevertheless, the application of antibiotics raises concerns regarding potential adverse effects such as antibiotic resistance and imbalances in the gut microbiota of bees. In response to these challenges, this study reviews the utilization of a probiotic-supplemented pollen substitute diet to promote honeybee gut health, enhance immunity, and overall well-being. We systematically explore various probiotic strains and their impacts on critical parameters, including survival rate, colony strength, honey and royal jelly production, and the immune response of bees. By doing so, we emphasize the significance of maintaining a balanced gut microbial community in honeybees. The review also scrutinizes the factors influencing the gut microbial communities of bees, elucidates the consequences of dysbiosis, and evaluates the potential of probiotics to mitigate these challenges. Additionally, it delineates different delivery mechanisms for probiotic supplementation and elucidates their positive effects on diverse health parameters of honeybees. Given the alarming decline in honeybee populations and the consequential threat to global food security, this study provides valuable insights into sustainable practices aimed at supporting honeybee populations and enhancing agricultural productivity.


Assuntos
Criação de Abelhas , Probióticos , Abelhas , Animais , Agricultura , Antibacterianos , Disbiose
13.
Expert Opin Drug Deliv ; 21(4): 627-638, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38682272

RESUMO

INTRODUCTION: Currently, cancer immunotherapy is widely used as a groundbreaking method that can completely cure advanced cancers. However, this new immunotherapy has the challenge of low patient response, which is often due to many patients' tumors having an immunosuppressive environment, known as cold tumors. AREAS COVERED: This review aims to introduce various nanomedicine-derived combinational cancer immunotherapy that can transform cold tumor into hot tumors. Initially, we discuss new technologies for combinational immunotherapy based on multifunctional nanomedicines that can deliver combinational immunogenic cell death (ICD) inducers, immune checkpoint blockades (ICBs) and immune modulators (IMs) to targeted tumor tissues at the same time. Ultimately, we highlight how multifunctional nanomedicines for combinational cancer immunotherapy can be used to transform cold tumor into hot tumors against advanced cancers. EXPERT OPINION: Nanomedicine-derived combinational cancer immunotherapy for delivering multiple ICD inducers, ICBs, and IMs at the same time is recognized as a new potential technology that can activate tumor immunity and simultaneously increase the therapeutic efficacy of immune cells that can transform effectively the cold tumors into hot tumors. Finally, nanomedicine-derived combinational cancer immunotherapy can solve the serious problems of low therapeutic efficacy that occurs when treating single drug or simple combinational drugs in cancer immunotherapy.


Assuntos
Imunoterapia , Nanomedicina , Neoplasias , Humanos , Imunoterapia/métodos , Nanomedicina/métodos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Morte Celular Imunogênica/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Agentes de Imunomodulação/administração & dosagem , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/química , Agentes de Imunomodulação/farmacologia , Microambiente Tumoral , Terapia Combinada
14.
Front Immunol ; 15: 1380049, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576607

RESUMO

Introduction: There is currently no vaccine against Chagas disease (ChD), and the medications available confer multiple side effects. Mycobacterium bovis Bacillus Calmette-Guérin (BCG) produces balanced Th1, Th2, and Th17 modulatory immune responses and has improved efficacy in controlling chronic infections through nonspecific immunity. We aimed to improve the response to infection by inducing a stronger immune response and greater protection against the parasite by trained immunity. Methods: BALB/c mice were immunized with BCG subcutaneously, and 60 days later, they were infected with Trypanosoma cruzi intraperitoneally. An evaluation of the progression of the disease from the acute to the chronic stage, analyzing various aspects such as parasitemia, survival, clinical status, and humoral and cellular immune response, as well as the appearance of visceral megas and the histopathological description of target organs, was performed. Results: Vaccination reduced parasitemia by 70%, and 100% survival was achieved in the acute stage; although the presentation of clinical signs was reduced, there was no increase in the antibody titer or in the differential production of the isotypes. Conclusion: Serum cytokine production indicated a proinflammatory response in infected animals, while in those who received BCG, the response was balanced by inducing Th1/Th2-type cytokines, with a better prognosis of the disease in the chronic stage.


Assuntos
Doença de Chagas , Mycobacterium bovis , Animais , Camundongos , Vacina BCG , Parasitemia , Infecção Persistente , Adjuvantes Imunológicos
15.
Cureus ; 16(1): e53188, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38425632

RESUMO

Background The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design The RBAC-QoL study, a double-blind, randomised, controlled pilot feasibility study, aimed to determine RBAC's effects on QoL and the associated action mechanisms. Primary outcomes were the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods Participants were adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions were RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data was collected from five study visits six weeks apart. The trial remained ongoing as of December 2023. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance was observed and adjusted with covariates. Results Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F1,8 = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at Week 6 (p = 0.032, Cohen's d = 1.454) and marginally at Week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (Week 18) and total protein (Weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson's r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups.  Conclusions RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway - these findings, though preliminary, are valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

17.
Inflamm Intest Dis ; 9(1): 1-10, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298887

RESUMO

Introduction: Whether white blood cell (WBC) counts are predictors for the effectiveness of thiopurine treatment in ulcerative colitis (UC) has been inconclusive in previous studies with small sample sizes. We investigated the association between WBC counts and future relapses in UC patients in a large-scale multi-center study. Methods: This retrospective cohort study enrolled a total of 723 UC patients in remission from 33 hospitals and followed up for 3 years. Relapse was defined as a need for treatment intensification. The risk of relapse was compared among patients with the baseline WBC counts <3,000/µL (N = 31), 3,000-4,000/µL (N = 167), 4,000-5,000/µL (N = 241), and ≥5,000/µL (N = 284) using a Cox regression model analysis. Moreover, exploratory analyses were conducted to identify other factors predicting relapse. Results: During a median follow-up period of 1,095 (interquartile range, 1,032-1,119) days, relapse occurred in 17.2% (125/723). In a crude analysis, WBC counts were not associated with relapse; hazard ratios (HRs) (95% confidence interval [CI]) were 1.50 (0.74-3.06), 1.02 (0.66-1.59), and 0.67 (0.43-1.05) in WBC <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively (WBC ≥5,000/µL group, as reference). Multivariable-adjusted analyses showed similar results; HRs (95% CI) were 1.21 (0.59-2.49), 1.08 (0.69-1.69), and 0.69 (0.44-1.07), in <3,000/µL, 3,000-4,000/µL, and 4,000-5,000/µL groups, respectively. In the exploratory analyses, thiopurine use <1 year and a mean corpuscular volume <90 fL were predictors for relapse. Discussion/Conclusion: WBC counts were not predictors for future relapses in patients with UC treated with thiopurine as a maintenance therapy.

18.
Health Sci Rep ; 7(2): e1884, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38352696

RESUMO

Background: The effect of pain genes (NAV1, EHMT2, SP1, SLC6A4, COMT, OPRM1, OPRD1, CYP2D6, and CYP3A4) have not been reported previously in kidney renal clear cell carcinoma (KIRC) patients and thus we made a comprehensive analysis of pain genes in the prognosis of KIRC and tumor immunotherapy. Methods: In this study, TCGA, Kaplan-Meier plotter, Metascape, STRING, Human Protein Atlas, Single Cell Expression Atlas database, LinkedOmics, cBioPortal, MethSurv, CancerSEA, COSMIC database and R package (ggplot2, version 3.3.3) were used for comprehensive analysis of pain genes in KIRC. Pearson and Spearman correlation coefficients were for co-expression analysis. Immunotherapy and TISIDB database were used for tumor Immunotherapy. Results: Representative pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4) were statistically significant (p < 0.0001) in the prognosis of KIRC. Immunotherapy (anti-PD-1 therapy, anti-PD-L1 therapy, and anti-CTLA4 therapy) and immunomodulator (immunoinhibitor, immunostimulator, and MHC molecule) in KIRC were significant associated with pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4), which were the important addition to clinical decision making for patients. Conclusions: Our study uncovered a mechanism for the effect of pain genes on KIRC outcome via the modulation of associated co-expression gene networks, gene variation, and tumor Immunotherapy.

19.
Acta Pharm Sin B ; 14(2): 765-780, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322349

RESUMO

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated ß-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile ß-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38375842

RESUMO

BACKGROUNDS: Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities. METHODS: This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach meaningful a conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects. RESULTS: Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy. CONCLUSION: These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

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