Indian Journal of Clinical Biochemistry最新文献

Methotrexate is used to manage moderate to severe psoriasis and psoriatic arthritis. Methotrexate acts by inhibiting the enzymes involved in nucleotide synthesis. Methotrexate polyglutamates (MTXPGs) have a higher potency to inhibit Dihydrofolate reductase (DHFR), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC), and thymidylate synthase (TS), compared to naïve methotrexate. Among all the MTXPGs, methotrexate polyglutamate three (MTXPG-3) is a more potent inhibitor of DHFR, ATIC, and TS enzymes. MTXPG-3 is anticipated to allow therapeutic drug monitoring in immune-mediated inflammatory diseases. We aim to study MTXPG-3 levels as a biomarker for both efficacy and adverse events among psoriatic patients treated with methotrexate monotherapy. We used the LC-MS/MS (Liquid Chromatography Mass Spectrophotometry) system for measuring erythrocyte MTXPG-3. We recruited 106 patients with psoriasis who were treated with methotrexate. Sixty-one of them had psoriatic arthritis (concomitant or in the past). The mean age was 45.08 ± 13.04 years. After twenty-four weeks of methotrexate treatment, 73(69%) were responders, and 33(31%) were non-responders. Thirty-nine (36%) experienced adverse effects, and 67(64%) did not experience any adverse effects. We observed a significant positive correlation between erythrocyte MTXPG-3 and methotrexate dose per week at weeks 12 and 16 but not at week 24. Erythrocyte MTXPG-3 did not correlate with response or adverse effects. It can be used as a marker of compliance.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-024-01269-x.

Many studies showed Vitamin D deficiency is highly prevalent in healthy individuals. We planned to study the normal levels of Vitamin D in healthy individuals and make recommendation for defining deficiency of 25(OH)D in Indian population. Normal healthy subjects 18 to 60 years of age were included. Estimation of serum calcium, serum phosphorus, iPTH and bone alkaline phosphatase levels with vitamin D (25(OH)D) levels were done to study the normal 25(OH)D levels and make recommendation for defining deficiency of 25(OH)D in Indian population. Meta-analysis was performed of studies which estimated the mean vitamin D levels in healthy individuals. There was significant positive correlation of serum 25(OH)D levels with calcium levels (r = 0.148; p-value = 0.003). The normal mean values of 25(OH)D levels in total population was 13.5 ± 7.83 ng/ml, iPTH was 59.8 ± 28.84 pg/ml, bone ALP was 14.6 ± 6.66 microg/ml. The normal upper bound of 25(OH)D in 97.5% of total population in our study is less than 33.19 ng/ml. The normal upper bound of iPTH and bone ALP in 97.5% of total population in our study was less than 123.97 pg/ml and 32.19 microg/ml, respectively. Pooled analysis of 33 studies revealed overall mean 25(OH)D levels in total population to be 13.95 ng/ml (95%CI - 12.37-15.54). The concept of initializing treatment based on serum Vitamin D levels using the RDA (20ng/ml) and EAR (16ng/ml) values as "cutoff-points" is not recommended as per Institute of Medicine Committee on Dietary Reference Intakes, Washington DC. Vitamin D levels less than 12.5ng/ml in a symptomatic individual should be the sole criteria for treatment rather than Vitamin D levels alone. Trial Registration: CTRI/2018/02/011820; CTRI/2018/02/011913.

The increasing incidence of gastric cancer (GC) in the Kashmir Valley is concerning, but its root causes are largely unknown. Dysregulated activation of the Hedgehog signaling pathway has been linked to various cancers, and the Human Hedgehog Interacting Protein (HHIP), a tumor suppressor, is frequently dysregulated in malignancies. However, the expression of the HHIP gene in GC is inconsistent and poorly understood. This study aimed to examine HHIP gene expression in gastric cancer. We used methylation-specific PCR, Western Blot analysis, and quantitative reverse transcription PCR (qRT-PCR) to assess the hypermethylation and expression levels of HHIP gene promoters. The correlation between these results and clinical parameters (e.g. age, gender, histological type, class, stage, and lymph node metastasis) was studied with samples from 53 GC patients confirmed by histology. In 69.81% (37 out of 53) of the tumor tissue, HHIP hypermethylation was found. Of the 45 cases examined for mRNA expression, 53.33% (24 out of 45) showed a decrease in the HHIP mRNA level compared to the normal sample. In addition, 49.05% (26 out of 53) showed a decline in the expression of HHIP proteins. Almost all GC samples with reduced protein expression also showed a reduction in mRNA levels. These results suggest that the hypermethylation of the HHIP promoter leads to a decrease in the regulation of HHIP, which contributes to the activation of the hedgehog signal path and may play a critical role in the progress of GC. Our study highlights the significant link between HHIP hypermethylation and reduced gene expression at both mRNA and protein levels, suggesting that target HHIP gene methylation could be a promising treatment strategy for gastric cancer.

The first two vaccines administered in the COVID-19 vaccination campaign of India were Covaxin (BBV152) and Covishield (ChAdOx1-nCoV-19). In this study, we evaluate the longevity and sustainability of the humoral immune response after vaccination and various factors influencing it. An observational study was conducted in individuals who received both doses of Covaxin or Covishield vaccine, and their blood samples were analyzed for total-antiRBD-SARS-CoV-2 antibodies. Then, antibody titers were classified based on monthly time-intervals up to 360 days and their trend was analyzed. In addition, the correlation between antibody titers and factors such as previous SARS-CoV-2-infection status, vaccine type and presence of comorbidities was examined. Of the 2069 participants, most (1767;85.4%) had been vaccinated with Covaxin, but the higher antibody titers were induced by Covishield vaccine at all time points. However overall, antibodies persisted for at least 1 year, although a drop in antibody titers occurred in the 3rd and 6th months. In addition, 430 (20.8%) participants had prior SARS-CoV-2 infection (hybrid immunity) with a significantly higher humoral immune response compared with vaccine-induced immunity (naive immunity). No significant differences were observed in antibody titers related to age, sex and presence of comorbidities. We concluded that vaccine-mediated immunity lasts for at least one year. However, antibody titers decrease over time, which may be more pronounced in certain groups such as Covaxin vaccine, vaccine-induced-immunity, presence of comorbidities and > 60 years which should be considered when recommending booster vaccination, as these individuals may have a stronger and longer-lasting immune response to the virus.

Oral cavity cancer poses a significant health threat due to its aggressive nature and limited responsiveness to traditional therapies like chemotherapy and radiation, highlighting the need for more effective treatment options. To address this, researchers have explored a novel approach using niosome nanoparticles to co-encapsulate curcumin (CUR) and cisplatin (Cis), to enhance therapeutic efficacy. While CUR has anti-cancer properties, its poor bioavailability limits its effectiveness. Cis, on the other hand, is hindered by severe side effects and resistance. A dual-drug delivery system that encapsulates both CUR and Cis in niosome nanoparticles seeks to leverage the synergistic effects of these agents to improve treatment outcomes. The study synthesized Cis and CUR co-loaded nanoparticles (Cis/CUR-NPs) using reverse microemulsion and film dispersion methods, resulting in nanoparticles with an average size of 220.9 nm and a consistent size distribution. In vitro experiments demonstrated that the nanosized Cis/CUR-NPs could release both Cis and CUR, achieving a synergistic effect on OECM-1 cells at an optimal ratio (1:6) of the two drugs. Overall, the findings suggest that Cis/CUR-NPs offer a promising and effective strategy for leveraging the synergistic effects of Cis and CUR in treating oral cancer.

[This corrects the article DOI: 10.1007/s12291-022-01074-4.].

Prostate cancer is the World's second most frequent malignancy, with the fifth-highest male mortality rate. In advanced prostate cancer patients, point mutations such as T877A and W741L are prevalent, imparting treatment resistance and hence promoting cancer development. The emergence of drug resistance in prostate cancer necessitates the development of suitable ligands to allow for stronger interactions with the receptors, which can inhibit cancer progression. The present study focuses on flavonoids produced by plants, which may act as inhibitors of point mutations like T877A and W741L in prostate cancer. This research was conducted using an in-silico method where the compound Glabranin and its derivatives were virtually screened to identify potential drugs for combating such point mutations. Thirty-five Molecular Dockings were performed to find the ligand-receptor complexes with the lowest binding energy. Moreover, employing a variety of tools, ligands were evaluated for drug-likeness and toxicity, indicating a promising drug candidate. Based on the results of Molecular Docking, Drug-likeness, and ADMET testing, eight structures were subjected to a 100 ns Molecular Dynamics simulation. A QSAR analysis was also performed based on the simulation findings. In this study, it was revealed that GlaMod2 phytocompound was effective against T877A and W741L mutations in prostate cancer. It was observed that the phytocompound was stable and had potential properties for the development of a novel drug to combat prostate cancer and drug resistance This phytocompound may therefore be effective in the development of prostate cancer inhibitors for patients with mutant androgen receptors.

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Supplementary information: The online version contains supplementary material available at 10.1007/s12291-023-01134-3.