This study investigated alterations in serum tryptophan–kynurenine (TRP–KYN) metabolites and trimethylamine N-oxide (TMAO) levels associated with ground grape seed supplementation in individuals with nonalcoholic fatty liver disease (NAFLD) using a non-placebo-controlled, non-randomized, open-label, single-arm intervention design. Thirty NAFLD patients and thirty healthy control participants, matched for age and sex, were enrolled; the control group served solely as a baseline comparison and did not receive supplementation. NAFLD patients consumed 5 g of ground grape seeds daily on an empty stomach during two 25-day treatment periods separated by a 10-day interval. Serum samples were collected at baseline and at the end of each treatment period. Metabolite profiling was conducted using liquid chromatography–tandem mass spectrometry. At baseline, serum tryptophan and kynurenine levels in NAFLD patients were significantly lower than those in the control group (FDR-adjusted p = 0.003 for both); levels of 3-hydroxykynurenine, kynurenic acid, and 3-hydroxyanthranilic acid were also significantly lower. In contrast, the KYNA/KYN and QA/KYN ratios were significantly higher, while the KYNA/QA and 3-HAA/3-HK ratios were significantly lower (all q ≤ 0.004). TMAO levels did not differ between groups (q = 0.965). In longitudinal analyses of the NAFLD group, tryptophan levels remained unchanged, while KYN, 3-HK, KYNA, and QA levels, as well as the KYNA/KYN and KYNA/QA ratios, decreased, and the QA/KYN ratio and TMAO levels increased. For all these parameters, the overall time effect was significant after FDR correction (q < 0.05). Owing to the uncontrolled, non-randomized design, these within-group changes cannot be causally attributed to the supplement and may reflect regression to the mean or unmeasured confounding. These preliminary, hypothesis-generating findings indicate a potential association between ground grape seed supplementation and changes in TRP–KYN pathway metabolites and TMAO levels in NAFLD, underscoring the need for validation in adequately powered, randomized, and placebo-controlled trials.
Periodontal diseases are common inflammatory conditions that affect tissues supporting the teeth, including the gingiva, bone, and ligaments. If left untreated, they can lead to tooth loss and have been linked to more severe systemic inflammation. Saliva, which contains a variety of biological substances, provides a non-invasive method for studying oral and general health. Hyperlipidemia, a condition marked by high levels of cholesterol, triglycerides, and LDL, along with low HDL, is associated with cardiovascular disease. Malondialdehyde (MDA), a byproduct of lipid peroxidation, is often used as a marker of oxidative stress. Lipopolysaccharides (LPS), which are bacterial toxins, also play a role in the development of periodontitis. The aim of the study explores the link between salivary lipid levels and periodontitis and investigates whether MDA levels in saliva could reflect disease presence. Forty individuals took part in this study. Twenty had healthy gingiva, while the other twenty were diagnosed with periodontitis. Each participant underwent a full periodontal checkup, including measures like plaque and gingival indices, bleeding on probing, pocket depth, and attachment loss. Saliva samples were collected to measure lipid profiles and MDA levels. Those with periodontitis had significantly higher levels of total cholesterol, triglycerides, LDL, and MDA in their saliva. HDL was lower compared to the healthy group. The findings suggest a possible connection between high lipid levels and gingiva disease. MDA may be a useful marker for oxidative stress in people with periodontitis.
The coronary artery disease is prevalent among young population. This study evaluated the associations between dietary intakes, sociodemographic and lifestyle factors with lipid profile in young adults with premature coronary artery disease (PCAD). This cross-sectional study included 141 individuals with PCAD. Sociodemographic, lifestyle, dietary, anthropometric, and biochemical profiles were assessed. Statistical analyses included chi-square tests, t-tests, and regression modeling. The mean age was 30 ± 3.9 years. Among participants, 66
Background: Coronary artery disease (CAD) severity is influenced by metabolic and biochemical risk factors, which may differ by sex. The present study evaluated sex-based differences in biochemical and anthropometric parameters across single-, double-, and triple-vessel CAD. Methods: This cross-sectional study included 100 adults with angiographically confirmed CAD. Based on coronary angiography, patients were classified as having single-vessel disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD). Data analysis was performed using independent t-tests. A p-value < 0.05 was considered statistically significant. Results: Multivessel disease was highly prevalent, with DVD observed in 66
Atherosclerotic plaque rupture results from inflammatory amplification and extracellular matrix degradation rather than lipid accumulation alone. The quantitative contribution of immunometabolism reprogramming to plaque instability remains insufficiently defined. We investigated whether hexokinase-2 (HK2)–mediated glycolytic activation of CD4⁺ T cells function as a mechanistically relevant contributor to plaque destabilization. CD4⁺ T cells were isolated from carotid endarterectomy specimens (n = 120; stable n = 60, unstable n = 60). HK2 expression, enzyme kinetics, metabolic flux, cytokine secretion, MMP-9 activity, and collagen content were quantified and integrated into a nonlinear dynamical systems model. Unstable plaques exhibited a 2.31-fold increase in HK2 expression and a 54.8
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is common in people with Long COVID, including post-exertional malaise (PEM). The overlapping observation of PEM in pre- and post-COVID forms of ME/CFS suggests the potential for shared bioenergetic impairments, but this has not yet been demonstrated. Two cardiopulmonary exercise tests (CPET) administered 24 h apart can elucidate the metabolic underpinnings of each disease. This retrospective study examined physiological responses during two-day CPET in people with ME/CFS (63 females/21 males), Long COVID (52 females/27 males), and matched non-disabled control participants (51 females/20 males). Data were analyzed within sexes using repeated measures analysis of variance. All participants met maximal effort criteria. There were significant reductions in oxygen consumption ( V̇ O₂) and workload at the ventilatory anaerobic threshold (VAT) in both patient groups compared to non-disabled controls, with larger effect sizes at VAT than at peak exertion. Performance decrements were observed in both sexes. Females exhibited more pronounced abnormalities and significant group by test effects. No significant differences were observed between patient groups. Severe disability based on impaired V̇ O₂ was prevalent in both patient groups. Hemodynamic and ventilatory measures were within normal ranges. ME/CFS and Long COVID both involve a functionally significant bioenergetic failure complicated by inadequate post-exertional recovery, which is similar between the conditions and unexplained by hemodynamic and ventilatory changes. Findings support the utility of two-day CPET as an objective measure functional impairment in ME/CFS. Future studies may integrate mechanistic biomarkers with two-day CPET as trial endpoints and to establish likely responses to treatments for PEM.
Energy deficiency among exercising females is associated with metabolic adaptations to conserve energy, menstrual cycle disturbances, and poor bone health. The purpose of this paper is to describe how a randomized controlled trial (clinicaltrials.gov: NCT00392873) with a nutritional intervention influenced indicators of metabolic status and whether these indicators are associated with menstrual recovery among oligo/amenorrheic (Oligo/Amen) exercising women. Recreational and competitive female athletes with Oligo/Amen were randomized to a control group (Oligo/Amen Control, n = 36; 20.7 ± 0.5 yrs; 59.1 ± 1.3 kg; 21.3 ± 0.4 kg/m2) or an intervention group (Oligo/Amen + Cal, n = 40; 21.3 ± 0.5 yrs; 55.0 ± 1.0 kg; 20.4 ± 0.3 kg/m2), who increased energy intake 20–40
Premature coronary artery disease (PCAD) has emerged as a major public health concern in India, with onset occurring nearly a decade earlier than in Western populations and disproportionately affecting the young workforce. India bears a high burden of early-onset heart disease, driven by a complex interplay of genetic susceptibility, adverse dietary transitions, sedentary lifestyle, metabolic rearrangements, and socio-cultural determinants. This narrative review provides current evidence on the epidemiology, dietary and lifestyle factors, and mechanistic pathways underlying PCAD in Indian youth, highlighting the paradox of accelerated atherosclerosis despite comparatively modest elevations in traditional lipid markers. We examine how dietary patterns characterized by refined carbohydrates, trans fats, processed food, micronutrient deficiencies and erratic meal behaviours interact with metabolic risk factors such as dyslipidemia, obesity, hypertension, and diabetes mellitus to promote early endothelial dysfunction. Mechanistic insights are discussed with particular emphasis on dysregulation of one-carbon metabolism, oxidative stress, chronic inflammation, Apo B-mediated lipoprotein pathways, and epigenetic modifications that may predispose young Indians to premature atherosclerosis. The review also underscores gender specific vulnerabilities, underrepresentation of women in PACD research, and the contribution of familial and polygenic risk. We identify critical gaps in prevention, early screening, and evidence-based secondary care, and discuss future strategies, including personalized counselling and policy-level actions. Addressing PCAD in Indian youth requires a multidisciplinary approach combining mechanistic research, population-specific evidence, and public health interventions to safeguard the youth.
Omentin-1, an adipokine mostly released in stromal vascular portion of adipose tissue, contributes to inflammatory disorders. It improves energy homeostasis, cardiovascular function, glucose metabolism, and reduce oxidative stress. This study aims to evaluate levels of omentin-1, atherogenic indices, and high sensitive C-reactive protein as predictors of cardiovascular diseases in women with subclinical hypothyroidism (SCHT). Fifty newly diagnosed subclinical hypothyroid females and 40 healthy females matched in age with cases, are enrolled in present study. Thyroid function tests (TSH, FT3, and FT4) and Thyroid peroxidase antibody (A-TPO) were measured using electrochemiluminescence assay. Fasting blood glucose, lipid profile, and high sensitive C-reactive protein are analyzed by photometric measuring unit. Omentin-1 is analyzed by the Enzyme Linked Immunosorbent Assay (ELISA). Omentin-1 concentrations significantly decrease among women with SCHT compared to healthy controls. Furthermore, there is a significant elevation in Atherogenic indices (AIs), total cholesterol (TC), triglyceride (TG), low- density lipoprotein-cholesterol (LDL-c), very low-density lipoprotein-cholesterol (VLDL-c), and high sensitive C-reactive protein (hsCRP) among SCHT group. Omentin-1 showed a significant positive correlation with hsCRP, while a significant negative association found between omentin-1 and TSH as well as atherogenic index of plasma (AIP). ROC curve analysis for omentin-1 revealed it as potential biomarkers to predict development and progression of cardiovascular disease (CAD). The present study concluded that women with SCHT are more at risk of CVD and that omentin-1, atherogenic indices and hsCRP are potential biomarkers to predict development and progression of CAD in patients with subclinical hypothyroidism, thus requiring timely intervention. Atherogenic indices should be assessed in patients with normal lipid profile to enhance the evaluation of atherogenic risk.
Rheumatoid arthritis (RA) is the most prevalent form of inflammatory arthritis globally. It is believed to arise from a combination of genetic predisposition and environmental factors. Several investigations have emphasized the critical role of long non-coding RNAs (lncRNAs) in both the initiation and progression of RA. This study focuses on the potential link between the rs217727 and rs2839698 variants of the H19 and RA susceptibility. The study involved 152 patients with clinically confirmed RA and 150 age- and gender-matched controls. A kit was utilized to extract the DNA of all the samples. After preparing the samples, DNA genotyping was done by using the tetra-primer ARMS-PCR method. The multivariate logistic regression analysis indicated that individuals with the CT genotype of rs217727 have a 2.28 times greater risk of developing RA than those with the TT genotype (P = 0.016). Furthermore, a significant 1.96-fold increase in RA risk was observed in patients with the CT genotype compared with those with the CC + TT genotype (P = 0.003). In addition, the rs2839698 variant of the H19 was found to elevate the risk of RA within the co-dominant model (OR = 2.71, 95
Niemann-Pick disease type A (NPD-A) is a rare, autosomal-recessive lysosomal storage disorder caused by pathogenic variants in the SMPD1 gene. These variants lead to a deficiency of acid sphingomyelinase. This report describes an NPD-A case diagnosed in early infancy following the deaths of two siblings. A novel SMPD1 variant was identified in this case. A two-month-old female infant was referred to our institution with a preliminary diagnosis of NPD-A, prompted by a family history of sibling deaths. Physical examination revealed a flat nasal bridge and hepatosplenomegaly; otherwise, systemic findings were normal. The neurological examination was normal. Biochemical analysis revealed significantly reduced acid sphingomyelinase activity (2.1 nmol MU/mg protein/17 hours), which warranted further molecular investigation. Sequencing revealed a previously unreported homozygous frameshift variant in the SMPD1 gene (c.368del; p.N123Ifs*3) that was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Follow-up at four months showed progression of hepatosplenomegaly. The patient had achieved some developmental milestones. However, at ten months of age, she presented with acute respiratory distress and severe cyanosis. Despite receiving intensive care and ventilatory support, she died from her illness at 10.5 months of age. This case highlights the identification of a likely pathogenic variant in the SMPD1 gene associated with the severe infantile phenotype of NPD-A. The patient’s clinical presentation and disease course were consistent with the classic form of the disorder. These findings contribute to the expanding mutational spectrum of SMPD1 and emphasize the importance of early diagnosis in at-risk populations.
Parenteral nutrition is a specialized nutritional method for patients undergoing cancer treatment. It is used when patients struggle to eat due to side effects from chemotherapy or radiation. This method delivers nutrients directly into the bloodstream, bypassing the digestive system. Improving nutritional status before to surgery is crucial since malnutrition is linked to poor surgical outcomes. According to the univariate analysis, cancer therapies were the factors most strongly linked to shifts in the trend over time for role, emotional, and physical functioning. When enteral nutrition is insufficient or impractical for eligible cancer patients with chronic impairments in dietary intake or absorption, current recommendations prescribe home parenteral nutrition. The purpose of this review was to discuss how applied enteral nutrition affects cancer patients’ quality of life based on the findings of randomized controlled trials. This study indicates a possible survival benefit of CN treatment in metastatic cancer and emphasizes the need to enhance the evaluation of nutritional status in oncologic patients. Alongside interdisciplinary team members, this entails educating patients and caregivers on the immediate and long-term nutritional effects of planned treatments. Nutrition support can be administered orally, enterally, or parenterally, and dietitians are in charge of recommending, providing, and monitoring it.
Bone fractures are frequently occurring injuries, and their treatment often includes metal implants, which may require a second surgery for removal, causing pain and added costs. Bone adhesives have the potential to replace metal implants in the treatment of bone fractures. Advancing bone adhesive research requires a suitable in vivo model. Such a model should provide standardized osteotomy conditions in load-bearing bones, and enable quantitative assessment of multiple healing parameters (e.g., radiographic, biomechanical, histological). This study aimed to develop a standardized osteotomy model for testing bone adhesives. A transverse mid-shaft osteotomy of the right femur was performed in 3-month-old female Sprague-Dawley rats and stabilized with an intramedullary cannula. In vivo micro-computed tomography (micro-CT) scans were acquired weekly to monitor bone healing. After 12 weeks, the bones were analyzed biomechanically, histologically, and by ex vivo micro-CT. In vivo CT analysis demonstrated a progressive increase in bone volume, indicating ongoing healing. Histological staining revealed endochondral ossification, and bony bridging scores supported these findings. Biomechanical testing showed reduced bone strength compared to intact femora. These results suggest moderate stabilization with an intramedullary cannula, which provides borderline stability, making it a promising setup for assessing whether additional stabilization by bone adhesives could improve outcomes. In conclusion, we established a simple and reproducible rat model. Future studies may use this model to evaluate bone adhesives and to investigate their influence on fracture healing metabolism.
Osteoporosis is a major public health concern that occurs most commonly in postmenopausal women. The condition leads to decreased bone mineral density (BMD) and poor bone structure, which consequently increases the risk of fragility fractures (FFs). This process commonly stems from an imbalance in bone formation and resorption. Although antiresorptive therapies, especially bisphosphonates, are typically prescribed to reduce FF risk, the subcutaneous parathyroid analogue teriparatide, which stimulates bone formation, is more effective in reducing this risk. Teriparatide increases hip and spine BMD and reduces both vertebral and non-vertebral fracture risks. Although effective as monotherapy, teriparatide shows synergistic benefits when combined with denosumab or zoledronate. Teriparatide is well tolerated, with early safety concerns around osteosarcoma alleviated by long-term observational data and labelling updated accordingly. Data also suggest teriparatide is effective for the treatment of many off-label indications, such as non-union fractures and osteonecrosis of the jaw. Because of its unique mechanism of action, with plateauing of BMD gains after prolonged treatment, there is a 2-year prescribing limit set by the European Medicines Agency. Immediate sequential antiresorptive therapy after teriparatide is recommended in every patient. In patients previously exposed to bisphosphonates, the anabolic response to teriparatide is attenuated, particularly in the hip, likely due to prior suppression of bone remodeling. First-line use of teriparatide in Italy, however, is restricted to patients at very high fracture risk. A recent expert consensus suggested that the efficacy, safety and increased affordability of teriparatide support its use in a broader range of patients with FFs.
Pseudoacromegaly is a rare clinical entity characterized by acromegaloid features without growth hormone (GH) excess and with normal insulin-like growth factor 1 (IGF-1) levels. In adults, untreated primary hypothyroidism with pituitary hyperplasia (PH) is the only well-documented endocrine cause. PH may mimic a pituitary adenoma on neuroimaging, potentially leading to unnecessary surgery. We report the case of a 34-year-old woman presenting with progressive weight gain, coarse facial features, acral enlargement, anemia, menstrual irregularities, and symptoms of hypothyroidism. Laboratory evaluation revealed markedly elevated thyroid-stimulating hormone (TSH) (>150 mIU/mL), low free thyroxine (T4L) (0.15 ng/dL), normal IGF-1, and mild hyperprolactinemia. Pituitary magnetic resonance imaging (MRI) demonstrated symmetric enlargement with homogeneous enhancement and suprasellar extension, consistent with PH. A diagnosis of severe untreated primary hypothyroidism with pseudoacromegaly was established, and levothyroxine 150 μg/day was initiated. After 20 weeks, repeat MRI showed complete resolution of pituitary enlargement and clinical features. This case illustrates an uncommon presentation of severe hypothyroidism with combined pseudoacromegaly and PH. The pathophysiology involves chronic thyrotropin-releasing hormone (TRH) stimulation of thyrotrophs and lactotrophs, leading to pituitary enlargement and soft tissue changes due to glycosaminoglycan deposition. Recognition of this association is crucial, as thyroid hormone replacement can reverse both PH and acromegaloid features, avoiding unnecessary neurosurgical intervention. In patients presenting with acromegaloid features and pituitary enlargement, primary hypothyroidism should be considered. Prompt diagnosis and levothyroxine therapy can lead to complete clinical and radiological resolution.
