Purpose: The progressive nature of Type 2 diabetes mellitus (T2DM) due to declining pancreatic β-cell function frequently requires insulin dose optimization and intensification, resulting in high total daily doses (TDD) of insulin in clinical practice. However, evidence evaluating the relationship between TDD, body weight, and glycaemic control remains limited. Methods: A retrospective cohort study was conducted among adults with T2DM receiving insulin therapy at two primary health clinics between 2020 and 2023 (N=90). Patients were categorised into standard-dose insulin (SDI, n=44) and high-dose (HDI, n=46) insulin groups. The outcomes measured were changes in body weight and follow-up HbA1c. An independent-samples t test was performed to compare outcomes between dose groups and multivariable analyses was conducted to identify factors associated with body weight change and HbA1c. Results: Patients in the SDI group had a smaller mean body weight change than those in the HDI group (3.07±4.90 vs 5.57±6.69kg; mean difference −2.50 kg, 95% CI −4.95 to −0.05; p = 0.045). Mean follow-up HbA1c was higher in the HDI group (10.39±1.86%) compared with the SDI group (9.55±1.95%), with a between-group difference of −0.84% (95% CI −1.64 to −0.04; p = 0.040). TDD and pre-insulin body weight showed statistically significant associations with body weight change. Age, use of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors, insulin analogue, and mixed human/analogue regimens showed statistically significant associations with HbA1c. Conclusion: Higher insulin doses were associated with greater body weight change and higher HbA1c. However, prospective studies are needed to clarify temporal relationships and to formulate insulin optimization strategies.
Purpose Impaired sexual behavior associated with aging remains a significant global health concern. Studies are investigating natural compounds to identify effective interventions for counteracting this condition. The present study examined the effectiveness of sericin (Ser) on age-related sexual impairment in aged rats. Methods A total of 10 young adult and 40 aged male Wistar rats were used. The aged animals were categorized into four groups and received NS or Ser at doses of 200, 250, and 300 mg/kg for 30 consecutive days. Copulatory behavior was assessed to evaluate sexual function. At the end of the behavioral assessment, serum testosterone levels, penile p-PI3K/PI3K, p-Akt/Akt, p-eNOS/eNOS, and p-NF-κB/NF-κB ratios, oxidative stress markers (TAC, MDA, GPx, and SOD), as well as cGMP, NO, IL-6 and TNF-α levels were measured. Notably, biochemical evaluations (n = 6/group) and Western blotting (n = 3/group) were conducted on representative subsets. Results The results demonstrated that Ser improved copulatory behavior in aged animals. The enhancement in sexual behavior was associated with increased PI3K/Akt/eNOS signaling and restoration of the NO/cGMP pathway, elevated testosterone levels, reduced lipid peroxidation, increased TAC and antioxidant enzyme activities, as well as diminished penile levels of IL-6 and TNF-α in aged rats. Conclusion These findings suggest that the ability of Ser to attenuate oxidative stress and inflammation may represent a promising approach for restoring testosterone levels and PI3K/Akt/eNOS signaling, thereby alleviating age-related sexual dysfunction. Nevertheless, further studies are required to clarify the mechanisms and evaluate therapeutic potential of Ser in the management of sexual dysfunction associated with aging.
Purpose: Effective disease-modifying treatments for Alzheimer’s disease remain limited. We examined low-concentration nano-niosomal dimethyl fumarate (N-DMF) in an acute bilateral hippocampal amyloid-β25–35 rat model. Methods: DMF-loaded niosomes were characterized by electron microscopy, dynamic light scattering, zeta-potential measurement, encapsulation analysis, and in vitro release. Forty adult male Wistar rats were randomly allocated to Sham, Aβ, Aβ+DMF, or Aβ+N-DMF groups (n=10/group). Free DMF was given orally at 25 mg/kg on four alternate days; N-DMF delivered 1.5 mg DMF per rat per administration (approximately 5.0–6.0 mg/kg). Behavioral outcomes, hippocampal oxidative and inflammatory markers (n=6/group), immunoblot endpoints (n=3/group), and qualitative Congo red staining (n=3 in Sham and Aβ groups) were assessed. Results: The pre-filtration dispersion had a DLS Z-average of 404.6 nm, a polydispersity index of 0.316, a zeta potential of −34.0 mV, and 78.39% encapsulation efficiency. Compared with untreated Aβ-injected rats, N-DMF was associated with higher phospho-Nrf2, NQO1, and SOD activity; lower BACE1, phospho-NF-κB p65, calcineurin A, NFATC1, C1q, C3, MDA, TNF-α, and IL-6; and better performance in the measured behavioral endpoints. Conclusion: In this acute model, low-concentration N-DMF was associated with molecular, biochemical, and behavioral changes. These findings do not establish improved brain delivery, carrier-specific efficacy, or a causal relationship between Nrf2 signaling and behavioral outcomes.
Myocardial infarction (MI) is leading cause of cardiovascular morbidity and mortality in developed and developing countries. Deep insight into the cellular and molecular mechanisms governing cardiac infarction may foster the translation of emerging therapeutic approaches into clinical practice. The promotion of angiogenesis and blood perfusion into the ischemic myocardium is essential for restoring functional cardiomyocytes after infarction. It has been indicated that different immune cell subsets can regulate the angiogenic switch in ischemic myocardium via close interaction with vascular cells and production of various pro-angiogenesis cytokines. Natural killer cells are innate lymphocytes that may influence inflammatory and reparative responses after MI. Depending on their phenotype and the stage of injury, NK cells may aggravate tissue damage or contribute to repair. These cells have capacity to be recruited into the inured sites with the capacity to mediate several molecular and cellular mechanisms associated with healing process by collaborating with other immune cells, production of various cytokines. However, the precise role of NK cells in regulating angiogenesis following myocardial infarction remains incompletely understood. In this regard, the elucidation of NK cell function and activity may pave the way for the development of long-term, efficient therapeutics with minimal side effects in MI patients. Here, we aimed to collect the recent data related to the activity of NK cells within the ischemic myocardium and the regulatory role of these cells in healing processes.
