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World Journal of Gastroenterology May 2024The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of...
BACKGROUND
The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated.
AIM
To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC.
METHODS
We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.
RESULTS
The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs).
CONCLUSION
The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Antineoplastic Combined Chemotherapy Protocols; Middle Aged; Fluorouracil; Infusions, Intra-Arterial; Leucovorin; Aged; Adult; Hepatic Artery; Organoplatinum Compounds; Treatment Outcome; Molecular Targeted Therapy; Progression-Free Survival; Retrospective Studies; Immunotherapy; Combined Modality Therapy
PubMed: 38813052
DOI: 10.3748/wjg.v30.i17.2321 -
Turkish Journal of Medical Sciences 2023Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint...
BACKGROUND/AIM
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response.
MATERIALS AND METHODS
This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test.
RESULTS
The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells.
CONCLUSION
The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.
Topics: Humans; Arthritis, Rheumatoid; Methotrexate; Female; Male; Apyrase; Middle Aged; Antirheumatic Agents; Adult; Biomarkers; Treatment Outcome; Antigens, CD; Case-Control Studies; Aged; T-Lymphocytes
PubMed: 38813034
DOI: 10.55730/1300-0144.5672 -
Frontiers in Bioscience (Landmark... May 2024Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes... (Review)
Review
Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.
Topics: Humans; Choline; Non-alcoholic Fatty Liver Disease; Animals; Gastrointestinal Microbiome; Neoplasms; Liver Neoplasms; Lipid Metabolism
PubMed: 38812309
DOI: 10.31083/j.fbl2905182 -
Scientific Reports May 2024Tuberculosis (TB), caused by Mycobacterium tuberculosis, has a significant impact on global health worldwide. The development of multi-drug resistant strains that are...
Tuberculosis (TB), caused by Mycobacterium tuberculosis, has a significant impact on global health worldwide. The development of multi-drug resistant strains that are resistant to the first-line drugs isoniazid and rifampicin threatens public health security. Rifampicin and isoniazid resistance are largely underpinned by mutations in rpoB and katG respectively and are associated with fitness costs. Compensatory mutations are considered to alleviate these fitness costs and have been observed in rpoC/rpoA (rifampicin) and oxyR'-ahpC (isoniazid). We developed a framework (CompMut-TB) to detect compensatory mutations from whole genome sequences from a large dataset comprised of 18,396 M. tuberculosis samples. We performed association analysis (Fisher's exact tests) to identify pairs of mutations that are associated with drug-resistance, followed by mediation analysis to identify complementary or full mediators of drug-resistance. The analyses revealed several potential mutations in rpoC (N = 47), rpoA (N = 4), and oxyR'-ahpC (N = 7) that were considered either 'highly likely' or 'likely' to confer compensatory effects on drug-resistance, including mutations that have previously been reported and validated. Overall, we have developed the CompMut-TB framework which can assist with identifying compensatory mutations which is important for more precise genome-based profiling of drug-resistant TB strains and to further understanding of the evolutionary mechanisms that underpin drug-resistance.
Topics: Mycobacterium tuberculosis; Mutation; Genome, Bacterial; Drug Resistance, Multiple, Bacterial; Rifampin; Antitubercular Agents; Isoniazid; Tuberculosis, Multidrug-Resistant; Humans; Bacterial Proteins; Whole Genome Sequencing; Microbial Sensitivity Tests
PubMed: 38811658
DOI: 10.1038/s41598-024-62946-8 -
The Journal of Dermatological Treatment Dec 2024Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.
METHODS
Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.
RESULTS
The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy ( = .0002) and incidence of postherpetic neuralgia ( = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups ( = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ ( > .05).
CONCLUSIONS
Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.
Topics: Humans; Herpes Zoster; Neuralgia, Postherpetic; Antiviral Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Incidence; Bromodeoxyuridine
PubMed: 38811010
DOI: 10.1080/09546634.2024.2355256 -
National Toxicology Program Technical... May 2024Triclosan is a broad-spectrum antimicrobial agent to which humans are widely exposed. Very limited data are available regarding the dermal toxicity and the carcinogenic...
Triclosan is a broad-spectrum antimicrobial agent to which humans are widely exposed. Very limited data are available regarding the dermal toxicity and the carcinogenic potential of triclosan. In this study, groups of 48 male and 48 female B6C3F1/N mice were untreated or were dermally administered 0 (vehicle), 1.25, 2.7, 5.8, or 12.5 mg triclosan/kg body weight/day (mg/kg/day) in 95% ethanol, 7 days per week for 2 years. Vehicle control animals received 95% ethanol only; untreated, naive control mice were not dosed. There were no significant differences in survival among the groups. The highest dose of triclosan decreased the body weights of mice in both sexes, but the decrease was ≤8%. (Abstract Abridged).
Topics: Animals; Triclosan; Female; Mice; Male; Anti-Infective Agents, Local; Administration, Cutaneous; Dose-Response Relationship, Drug; Body Weight; Carcinogenicity Tests; Mice, Inbred Strains; Carcinogens; Carcinogenesis
PubMed: 38809813
DOI: 10.22427/NTP-TR-604 -
Asian Pacific Journal of Cancer... May 2024Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained largely unchanged over a couple of decades. This study is designed to ascertain the outcome and safety of Methotrexate, Doxorubicin, and Cisplatin regimen for chemotherapy in osteosarcoma patients through the utilization of meta-analysis.
METHODS
We interrogated trials that compared the MAP regimen with other regimens as chemotherapy for osteosarcoma from several databases encompassing PubMed, Science Direct, and grey literature (Google Scholar) until December 2022. The analyzed outcomes including Event-Free Survival (EFS), Overall Survival (OS), Tumor Necrosis (TN) rate, and Adverse Event (AE) were then analyzed using RevMan 5.4 software in fixed or random effect models.
RESULTS
Our meta-analysis comprised 8 prospective articles that evaluated a cumulative number of 2920 OS patients. The analysis results indicated no meaningful difference in 5-year EFS (OR=0.99, 95% CI=0.77-1.27, [P = 0.91]) and neoadjuvant chemotherapy response (TN) (OR=0.76, 95% CI=0.49-1.17, [P = 0.22]) between the MAP and control groups. Furthermore, 5-year OS analysis revealed a significant association in the control group (OR=0.82, 95% CI=0.68-0.99, [P = 0.04]). However, the control group was associated with statistically meaningful AE compared to the MAP group, particularly in thrombocytopenia (OR=0.46, 95% CI=0.23-0.90, [P = 0.02]) and fever (OR=0.34, 95% CI=0.26-0.46, [P < 0.00001]).
CONCLUSION
The present meta-analysis showed that the MAP regimen remains preferable in treating osteosarcoma patients despite no significant outcome compared to the other regimens considering the less frequent AE in the MAP regimen.
Topics: Osteosarcoma; Humans; Methotrexate; Doxorubicin; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Patient Safety; Prognosis; Survival Rate; Treatment Outcome
PubMed: 38809621
DOI: 10.31557/APJCP.2024.25.5.1497 -
BMC Oral Health May 2024This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. (Comparative Study)
Comparative Study
OBJECTIVE
This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate.
METHODS
One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test.
RESULTS
Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively.
CONCLUSION
GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.
Topics: Animals; Rats; Xerostomia; Parotid Gland; Ki-67 Antigen; Methotrexate; Gum Arabic; Thiophenes; Caspase 3; Male; Rats, Wistar; Quinuclidines
PubMed: 38807094
DOI: 10.1186/s12903-024-04374-8 -
BMC Plant Biology May 2024Nanotechnology has demonstrated its vital significance in all aspects of daily life. Our research was conducted to estimate the potential of primed seed with chitosan...
BACKGROUND
Nanotechnology has demonstrated its vital significance in all aspects of daily life. Our research was conducted to estimate the potential of primed seed with chitosan nanoparticles in seed growth and yield by inducing plant secondary metabolism of Pancratium maritimum L. one of the important medicinal plants. Petri dish and pot experiments were carried out. Seeds of Pancratium maritimum L. were soaked in Nano solution (0.1, 0.5, 1 mg/ ml) for 4, 8, 12 h. Germination parameters (germination percentage, germination velocity, speed of germination, germination energy, germination index, mean germination time, seedling shoot and root length, shoot root ratio, seedling vigor index, plant biomass and water content), alkaloids and antioxidant activity of Pancratium maritimum L. were recorded and compared between coated and uncoated seeds.
RESULTS
Our results exhibited that chitosan nanopriming had a positive effect on some growth parameters, while it fluctuated on others. However, the data showed that most germination parameters were significantly affected in coated seeds compared to uncoated seeds. GC-MS analysis of Pancratium maritimum L. with different nanopriming treatments showed that the quantity of alkaloids decreased, but the amount of pancratistatin, lycorine and antioxidant content increased compared with the control.
CONCLUSIONS
Applying chitosan nanoparticles in priming seeds might be a simple and effective way to improve the quantity of secondary metabolites of Pancratium maritimum L. valuable medicinal plant.
Topics: Chitosan; Germination; Seeds; Nanoparticles; Seedlings; Alkaloids; Antioxidants; Secondary Metabolism; Amaryllidaceae
PubMed: 38807068
DOI: 10.1186/s12870-024-05148-8 -
Scientific Reports May 2024The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in...
The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.
Topics: Female; Animals; Phenylacetates; Vagina; Mice; Humans; Chryseobacterium; Candida albicans; Symbiosis; Hydrogen-Ion Concentration; Gardnerella vaginalis; Disease Models, Animal; Vaginitis
PubMed: 38806600
DOI: 10.1038/s41598-024-62947-7