Category: Nevin Manimala

Front Pharmacol. 2025 Apr 7;16:1542560. doi: 10.3389/fphar.2025.1542560. eCollection 2025.

ABSTRACT

Metals have long held a significant role in the human body and have been utilized as mineral medicines for thousands of years. The modern advancement of metals in pharmacology, particularly as metallodrugs, has become crucial in disease treatment. As the machanism of metallodurgsare increasingly uncovered, some metallodrugs are already approved by FDA and widely used in treating antitumor, antidiabetes, and antibacterial. Therefore, a thorough understanding of metallodrug development is essential for advancing future study. This review offers an in-depth examination of the evolution of mineral medicines and the applications of metallodrugs within contemporary medicine. We specifically aim to summarize the historical trajectory of metals and mineral medicines in Traditional Chinese Mineral Medicine by analyzing key historical texts and representative mineral medicines. Additionally, we discuss recent advancements in understanding metallodrugs’ mechanisms, such as protein interactions, enzyme inhibition, DNA interactions, reactive oxygen species (ROS) generation, and cellular structure targeting. Furthermore, we address the challenges in metallodrug development and propose potential solutions. Lastly, we outline future directions for metallodrugs to enhance their efficacy and effectiveness. The progression of metallodrugs has broadened their applications and contributed significantly to patient health, creating good healthcare solutions for the global population.

PMID:40260378 | PMC:PMC12010122 | DOI:10.3389/fphar.2025.1542560

Front Pharmacol. 2025 Apr 7;16:1505674. doi: 10.3389/fphar.2025.1505674. eCollection 2025.

ABSTRACT

BACKGROUND: Multidrug-resistant bacteria are associated with a high number of deaths and pose a significant global concern. In recent decades, among these resistant bacteria, Enterococcus faecium, a hospital-acquired pathogen, has attracted more attention.

OBJECTIVE: The present study aims to document the current state of resistance in E. faecium globally by considering several variables, including geographical locations, temporal trends, and sources of infection.

METHODS: We searched studies in PubMed, Scopus, and Web of Science (30 November 2022). All statistical analyses were carried out using the statistical package R.

RESULTS: Our meta-analysis of antibiotic resistance across various clinical isolates revealed substantial heterogeneity and variability. The average resistance proportions ranged from 2% for linezolid to 62.8% for erythromycin, with significant differences observed across different time periods, countries, and World Health Organization regional offices.

CONCLUSION: Our findings confirm the high antibacterial activity of linezolid against E. faecium isolates. Additionally, our investigation reveals a gradual increase and a concerning upward trend in resistance rates for nearly all agents in recent years. However, the significant reduction in resistance rates for certain antibiotics suggests that these drugs could potentially regain their effectiveness in the future.

PMID:40260375 | PMC:PMC12009923 | DOI:10.3389/fphar.2025.1505674

Front Pharmacol. 2025 Apr 7;16:1534748. doi: 10.3389/fphar.2025.1534748. eCollection 2025.

ABSTRACT

INTRODUCTION: Tiebangchui (TBC, Tibetan name: བང་ང་ནག་པ།), the dried tuberous root of Aconitum pendulum Busch. and Aconitum flavaum Hand.-Mazz., is a prevalent used Tibetan medicine, recognized for its significant therapeutic effects despite its high toxicity. It is commonly employed in treating the diseases categorized as “Long” (རླུང་ནད།), cold, “Huang-shui” (སེར་ཆུ་ནད།), leprosy, and mania in Tibetan medicine. Notably, it is utilized in the treatment of rheumatoid arthritis, which is classified under the “Huang-shui” disease category according to Tibetan medical theory. Given its considerable toxicity, various processing techniques aimed at reducing the harmful effects of TBC are essential for its safe application in clinical settings. Hezi-decoction-processed method is a distinctive and effective traditional processing method of Tibetan medicine, but the overall variability of chemical constituents in the Hezi-decoction-processed TBC is still unclear. This investigation sought to examine a variety of diterpenoid alkaloids and tanning constituents, identify potential metabolic markers for differentiating the unprocessed TBC and Hezi-decoction-processed TBC at varying processing times, and determine the optimal processing time for reducing toxicity and maintaining efficacy.

METHODS: A combination of metabolomic techniques was developed, integrating ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) with desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) coupled with quantitative analytical techniques. This was done with the objective of monitoring the dynamic alterations in chemical constituents in TBC during the processing time. Metabolic markers were observed via DESI-MSI, and three alkaloids and five tannin acids were quantified through the use of UPLC and HPLC.

RESULTS: Fifty-one compounds were identified in unprocessed TBC and processed samples, of which 31 were discernible from unprocessed TBC. A total of 22 metabolic markers, such as aconine, aconitine, benzoylaconine, chebulic acid, gallic acid, and corilagin, can proficiently distinguish between raw and processed TBC with different processing times. And the results of content determination of three alkaloids and five tannins showed that they were stabilized at 72 h. The monoester-diterpenoid alkaloids (MDAs) and diester-diterpenoid alkaloids (DDAs) levels were 0.0149% and 0.0852% in 72 h, respectively. The contents of gallic acid, corilagin, 1,2,3,4,6-O-pentagalloylglucose, chebulinic acid, and ellagic acid were 8.9706, 9.3444, 1.2438, 5.7582, and 3.1160 mg/g, respectively. The distribution and accumulation of metabolic markers during processing were investigated by DESI-MS. The results of DESI-MSI were consistent with those of content determination experiments. Combined with the multivariate statistical analysis, content determination of three alkaloids and five tannin acids and DESI-MSI, 72 h is demonstrated to be the appropriate time for toxicity attenuation and efficacy reservation of TBC.

DISCUSSION: The implementation of this technique could contribute to the identification of markers in Hezi decoction-processed TBC and the establishment of effective quality control and evaluation procedures to ensure the safety of TBC. The proposed method has the potential to elucidate the processing mechanism of Aconitum medicines and other toxic traditional Chinese medicines, given its wide applicability.

PMID:40260374 | PMC:PMC12009863 | DOI:10.3389/fphar.2025.1534748

Cureus. 2025 Mar 21;17(3):e80967. doi: 10.7759/cureus.80967. eCollection 2025 Mar.

ABSTRACT

Objective Patients undergoing below-knee amputation may experience considerable postoperative mortality risk, particularly in the presence of comorbid conditions. The aim of this study was to present a newly developed risk index and scoring system to predict one-year mortality, morbidity, and functional independence in patients undergoing below-knee amputation. Materials and methods One-year postoperative follow-up data were obtained retrospectively from 30 patients who underwent below-knee amputation at our clinic. A novel scoring system was developed using variables including age, preoperative systemic diseases, diabetic foot infection, previous extremity surgery, postoperative mobilization time, and early complications. Survival analysis was performed, and functional independence was assessed using the Katz Activities of Daily Living Scale (Katz scores). The relationship between patients’ survival status and Katz scores with the developed risk index was statistically evaluated. Results The average age of the patients was 71.7 years. Survival analysis indicated that higher scores on the newly developed index were significantly associated with increased mortality and morbidity (p<0.05). There was also a strong negative correlation between patients’ scores and Katz scores (r=-0.757; p<0.001), indicating that patients with higher risk scores experienced poorer functional outcomes. Conclusions This retrospective study introduced a novel scoring system that reliably predicts functional independence in patients following below-knee amputation. However, its accuracy in predicting mortality and morbidity remains limited. Further refinement and validation in larger patient populations are required to enhance predictive accuracy and clinical applicability.

PMID:40260362 | PMC:PMC12010033 | DOI:10.7759/cureus.80967

Cureus. 2025 Mar 21;17(3):e80974. doi: 10.7759/cureus.80974. eCollection 2025 Mar.

ABSTRACT

Introduction Diabetes mellitus is a metabolic disorder characterized by abnormally high sugar levels in the blood for prolonged periods of time. The world’s largest number of diabetics resides in India, making it the world’s diabetic capital, with a diabetic foot ulcer (DFU) incidence of around 8-17%. Due to the polymicrobial and multidrug resistant (MDR) nature of DFUs, antimicrobial susceptibility testing is of high importance to help treat patients effectively and prevent the development of MDR bacteria. The ability to form biofilms is a significant additive to virulence of an organism that causes an able strain to be resistant to more antibiotics as compared to a free-living strain, thereby further delaying the healing of DFUs. Materials and methods This study included 74 samples collected from patients with DFUs, out of which 69 (93.24%) yielded growth on culture. Gram staining was done for the direct microscopy, isolation, and determination of organism, and the detection of biofilm formers using Congo Red Agar plates. Data were tabulated and statistically analyzed. Results Out of 74 samples collected, 69 (93.24%) yielded growth on culturing, with 5 (6.76%) cultures coming back negative. On Gram staining, 42 (56.8%) samples showed Gram-positive cocci and 53 (71.6%) showed Gram-negative bacilli. On isolating organisms from the samples, 16 (21.7%) samples had Pseudomonas aeruginosa, followed by Klebsiella pneumoniae at 13 (17.6%) and Proteus mirabilis and Escherichia coli at 11 each (14.9%), indicating a Gram-negative bacteria predominance. Of the Gram-positive bacteria isolated, Staphylococcus aureus stands at two (2.7%) and Streptococcus pyogenes at one (1.4%). The prevailing monomicrobiality could be attributed to antibiotic administration prior to sample collection. On antibiotic sensitivity of organisms tested against each antibiotic, more than 75% of tested samples were resistant to ampicillin, cefuroxime, and erythromycin, and around 70% and more of tested samples were sensitive to ertapenem, meropenem, amikacin, gentamicin, benzylpenicillin, vancomycin, and clindamycin. Out of the 69 positive cultures, 29 (42.03%) yielded biofilm formers. Pseudomonas aeruginosa was the predominant biofilm former with 10 (34.48%) of 29 of total biofilm-forming isolates, followed by E. coli and K. pneumoniae with five each (17.24%) and Proteus mirabilis with three samples (10.34%). Regarding strains forming biofilms according to bacterium species, S. aureus was predominant, with 100% (two out of two samples) of isolates forming biofilms. Staphylococcus aureus was followed by Pseudomonas aeruginosa with 62.5% (10 out of 16 samples), Acinetobacter baumannii (two out of four samples) and Enterobacter cloacae (one out of two samples) with 50% each, E. coli with 45.45% (5 out of 11 samples), and K. pneumoniae with 38.46% (5 out of 13 samples) of isolates forming biofilms. It should be noted that only two S. aureus, four A. baumannii, and two Enterobacter cloacae samples were isolated in comparison to a larger number of Gram-negative bacteria. This study has found that 100% of multidrug-resistant organisms (MDROs) are biofilm formers. Conclusion The ability to form biofilms adds immensely to the virulence and antibiotic resistance. Detection of biofilm formers is non-invasive and convenient to measure and would help provide insight into antibiotics to be administered to the patient, thereby reducing development of MDROs and reducing healing time.

PMID:40260359 | PMC:PMC12010084 | DOI:10.7759/cureus.80974

Cureus. 2025 Mar 21;17(3):e80976. doi: 10.7759/cureus.80976. eCollection 2025 Mar.

ABSTRACT

Background Plain language summaries (PLSs) make scientific research accessible to a broad non-expert audience. However, crafting effective PLS can be challenging, particularly for non-native English-speaking researchers. Large language model (LLM) chatbots have the potential to assist in generating summaries, but their effectiveness compared to human-generated PLS remains underexplored. Methods This cross-sectional study compared 30 human-written PLS with LLM chatbot (viz., ChatGPT (OpenAI, San Francisco, CA), Claude (Anthropic, San Francisco, CA), Copilot (Microsoft Corp., Washington, DC), Gemini (Google, Mountain View, CA), Meta AI (Meta, Menlo Park, CA), and Perplexity (Perplexity AI, Inc., San Francisco, CA)) generated PLS. The readability of the PLS was checked by the Flesch reading (FR) ease score, and understandability was checked by the Flesch-Kincaid (FK) grade level. Three authors rated the text on seven-item predefined criteria, and their average score was used to compare the quality of the PLS. Results In comparison to human-written PLS, chatbots could generate PLS with lower FK grade levels (p-value < 0.0001) and except Copilot, all others had higher FR ease scores. The overall score of human-written PLS was 8.89±0.26. Although there was statistically significant variance among the scores (F = 7.16, p-value = 0.0012), in the post-hoc test, there was no difference between human-generated and individual chatbots-generated PLS (ChatGPT 8.8±0.34, Claude 8.89±0.33, Copilot 8.69±0.4, Gemini 8.56±0.56, Meta AI 8.98±0.23, and Perplexity 8.8±0.3). Conclusion LLM chatbots can generate PLS with better readability and a person with a lower grade of education can understand it. The PLS are of similar quality to those written by human authors. Hence, authors can generate PLS from LLM chatbots and it is particularly beneficial for researchers in developing countries. While LLM chatbots improve readability, they may introduce minor inaccuracies also. Hence, PLS generated by LLM should always checked for accuracy and relevancy.

PMID:40260353 | PMC:PMC12010112 | DOI:10.7759/cureus.80976

Int J Health Plann Manage. 2025 Apr 21. doi: 10.1002/hpm.3939. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to illustrate the state of stroke care and rehabilitation in the Philippines through the perspectives of local government officials, policymakers, and organisational leaders. It sought to identify challenges, opportunities, and recommendations for improving stroke policies and services across different administrative levels.

METHODS: Mixed-methods approach involving a structured survey of 131 local government officials and in-depth interviews with eight key stakeholders. Survey participants included Department of Health (DoH) officials, local chief executives, policymakers, Local Government Unit (LGU) employees, and representatives from non-government agencies. Interviewees comprised leads and managers from the DoH and representatives from organisations including the Philippine Academy of Rehabilitation Medicine (PARM), Physicians for Peace Philippines, and the Philippine Council for Health Research and Development (PCHRD). Quantitative survey data were analysed using descriptive statistics and qualitative interview data were thematically analysed, then the two types of data were triangulated and organised by theme.

RESULTS: Findings revealed significant gaps in funding, healthcare infrastructure, and policy implementation. Challenges included inadequate facilities, lack of qualified staff, financial barriers, and regional disparities in service provision. Survey and interview participants emphasised the need for increased government support, comprehensive policies, and community-based rehabilitation (CBR) programmes. Improving stroke survivors’ quality of life was ranked as the most critical aspect of rehabilitation programmes.

CONCLUSIONS: The study highlights the critical need for more equitable and accessible stroke care and rehabilitation in the Philippines. This can be facilitated by sustained government support, inter-agency collaboration, community engagement, and the implementation of holistic, evidence-based, and cost-effective CBR initiatives.

PMID:40259445 | DOI:10.1002/hpm.3939

Int J Cancer. 2025 Apr 21. doi: 10.1002/ijc.35451. Online ahead of print.

ABSTRACT

Lynch-like syndrome (LLS) presents very similar clinicopathological characteristics to Lynch syndrome (LS) but the mechanism for cancer predisposition remains unknown. The present study aims to investigate the causal mechanism of LLS by a comprehensive genetic and epigenetic approach. Thirty-two LLS and 34 LS patients with colorectal cancer (CRC) fitting the Amsterdam and Bethesda criteria were included, along with 29 CRC sporadic patients, and analyzed for the presence of pathogenic variants in 94 genes associated with hereditary tumors. The cohorts were also characterized for the methylation profile and examined through a sample group analysis and a Stochastic Epigenetic Mutations (SEMs) analysis in comparison with 29 age-matched healthy controls. The multigene panel analysis revealed the presence of pathogenic variants in non-mismatch repair (MMR) genes and three variants classified as pathogenic/likely pathogenic possibly predisposing to LLS. The epigenetic analysis showed epivariations targeting genes associated with LS or DNA repair, most of them associated with the Fanconi Anemia pathway, which could explain the susceptibility to cancer. Our results highlight the need for using extended genetic and epigenetic analyses to understand the causal mechanism of LLS.

PMID:40259440 | DOI:10.1002/ijc.35451

Alzheimers Res Ther. 2025 Apr 21;17(1):86. doi: 10.1186/s13195-025-01738-2.

ABSTRACT

BACKGROUND AND OBJECTIVES: The association between obesity and young-onset dementia (YOD, defined as dementia diagnosed before age 65) is established, but the specific impact of abdominal obesity in women remains unclear. Abdominal obesity, driven by excess visceral fat, may increase dementia risk through metabolic and vascular pathways. We investigated the association between abdominal obesity and YOD risk in women using a large nationwide cohort.

METHODS: We analyzed 964,536 Korean women aged 40-60 years who underwent national health checkups in 2009. General obesity was defined by body mass index (BMI), and abdominal obesity was categorized by waist circumference (WC) into < 75 cm, 76-84 cm, 85-94 cm, and ≥ 95 cm. YOD was identified using ICD-10 codes and dementia medication prescriptions. Hazard ratios (HRs) for YOD were estimated using multivariable Cox proportional hazard models adjusted for lifestyle and clinical factors.

RESULTS: Over a median follow-up of 8.2 years, YOD incidence increased progressively with higher WC. Women with WC ≥ 95 cm had a 55% increased risk of YOD (HR 1.55; 95% CI 1.34-1.79) compared to those with WC < 75 cm. The association was particularly strong for vascular dementia (VD), with HR 1.83 (95% CI 1.30-2.57). By contrast, BMI showed a U-shaped relationship, with the lowest YOD risk observed in women with normal BMI (18.5-22.9 kg/m²), and significantly elevated risks in both underweight (BMI < 18.5 kg/m²; HR 1.39, 95% CI 1.13-1.71) and morbidly obese women (BMI ≥ 30 kg/m²; HR 1.26, 95% CI 1.10-1.45).

DISCUSSION: Abdominal obesity is a significant, independent risk factor for YOD in women, particularly for VD. These findings underscore the importance of addressing abdominal obesity in middle-aged women to reduce dementia risk.

PMID:40259430 | DOI:10.1186/s13195-025-01738-2

J Health Popul Nutr. 2025 Apr 21;44(1):130. doi: 10.1186/s41043-025-00870-x.

ABSTRACT

BACKGROUND: Tuberculosis (TB) is known to be a disease associated with underprivileged social conditions such as poverty, malnutrition, and overcrowding. Homeless individuals are at a higher risk of contracting TB due to factors such as substance misuse, alcohol disorder, smoking, and malnutrition. Recognizing this risk, the World Health Organization recommends TB screening in these vulnerable populations. As a result, this study aims to evaluate the prevalence of TB and its associated factors among people who experience homelessness living in Wolaita Zone Towns.

METHOD: A cross-sectional study was conducted on 352 homeless individuals with presumed TB from May 1 to July 30, 2023. Data was collected using pre-tested structured questionnaires. The symptom was assessed using WHO guidelines. Sputum samples were screened for TB using GeneXpert MTB/RIF assay technique and those found to be positive were confirmed via the Lowenstein-Jensen(LJ) culture method by comparing equal numbers of positives and negatives. The data was analyzed using statistical software packages (SPSS) version 26. Logistic regression analysis was used to identify factors associated with TB and a P-value of less than 0.05 at a 95% confidence interval was considered statistically significant.

RESULTS: The prevalence of bacteriological confirmed TB among homeless individuals was 7.7% [95% CI: 4.8- 10.5] and rifampicin-resistant TB (RR-TB) was not detected. Multivariate logistic regression analysis revealed that smoking cigarettes[AOR = 7.673, 95% CI: 1.622,36.303], smoking benzene[AOR = 8.348, 95% CI: 2.061,33.813], chewing tobacco [AOR = 4.138, 95% CI: 1.249,13.709], duration of being homeless[AOR = 6.749, 95% CI: 1.914, 23.797], taking any medication currently [AOR = 4.686, 95% CI:1.216,18.064], BMI [AOR = 5.328, 95% CI: 1.663,17.070] and having HIV infection [AOR = 5.234, 95% CI: 1.558, 17.585] were significantly associated with the prevalence of PTB in people who experience homelessnesss.

CONCLUSIONS: This study indicates a higher prevalence of pulmonary TB (PTB) in homeless individuals compared to the general population. It is strongly recommended to implement targeted TB preventive and control measures and actively monitor for the diseases within those vulnerable population.

PMID:40259425 | DOI:10.1186/s41043-025-00870-x