Associations between type 1 diabetes and pulmonary tuberculosis: a bidirectional mendelian randomization study.

BACKGROUND: Type 1 diabetes mellitus (T1DM) has been associated with higher pulmonary tuberculosis (PTB) risk in observational studies. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect between T1DM and PTB using bidirectional Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) of T1DM and PTB were extracted from the public genetic variation summary database. In addition, GWAS data were collected to explore the causal relationship between PTB and relevant clinical traits of T1DM, including glycemic traits, lipids, and obesity. The inverse variance weighting method (IVW), weighted median method, and MR‒Egger regression were used to evaluate the causal relationship. To ensure the stability of the results, sensitivity analyses assess the robustness of the results by estimating heterogeneity and pleiotropy. RESULTS: IVW showed that T1DM increased the risk of PTB (OR = 1.07, 95% CI: 1.03-1.12, P < 0.001), which was similar to the results of MR‒Egger and weighted median analyses. Moreover, we found that high-density lipoprotein cholesterol (HDL-C; OR = 1.28, 95% CI: 1.03-1.59, P = 0.026) was associated with PTB. There was no evidence of an effect of glycemic traits, remaining lipid markers, or obesity on the risk of PTB. In the reverse MR analysis, no causal relationships were detected for PTB on T1DM and its relevant clinical traits. CONCLUSION: This study supported that T1DM and HDL-C were risk factors for PTB. This implies the effective role of treating T1DM and managing HDL-C in reducing the risk of PTB, which provides an essential basis for the prevention and comanagement of concurrent T1DM and PTB in clinical practice.

Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. It has become a leading cause of death in patients with diabetes and end-stage renal disease. Ferroptosis is a newly discovered pattern of programmed cell death. Its main manifestation is the excessive accumulation of intracellular iron ion-dependent lipid peroxides. Recent studies have shown that ferroptosis is an important driving factor in the onset and development of DN. Ferroptosis is closely associated with renal intrinsic cell (including renal tubular epithelial cells, podocytes, and mesangial cells) damage in diabetes. Chinese herbal medicine is widely used in the treatment of DN, with a long history and definite curative effect. Accumulating evidence suggests that Chinese herbal medicine can modulate ferroptosis in renal intrinsic cells and show great potential for improving DN. In this review, we outline the key regulators and pathways of ferroptosis in DN and summarize the herbs, mainly monomers and extracts, that target the inhibition of ferroptosis.

The role of Chinese herbal medicine in the treatment of diabetic nephropathy by regulating endoplasmic reticulum stress.

Diabetic nephropathy (DN), a prevalent microvascular complication of diabetes mellitus, is the primary contributor to end-stage renal disease in developed countries. Existing clinical interventions for DN encompass lifestyle modifications, blood glucose regulation, blood pressure reduction, lipid management, and avoidance of nephrotoxic medications. Despite these measures, a significant number of patients progress to end-stage renal disease, underscoring the need for additional therapeutic strategies. The endoplasmic reticulum (ER) stress response, a cellular defense mechanism in eukaryotic cells, has been implicated in DN pathogenesis. Moderate ER stress can enhance cell survival, whereas severe or prolonged ER stress may trigger apoptosis. As such, the role of ER stress in DN presents a potential avenue for therapeutic modulation. Chinese herbal medicine, a staple in Chinese healthcare, has emerged as a promising intervention for DN. Existing research suggests that some herbal remedies may confer renoprotective benefits through the modulation of ER stress. This review explores the involvement of ER stress in the pathogenesis of DN and the advancements in Chinese herbal medicine for ER stress regulation, aiming to inspire new clinical strategies for the prevention and management of DN.

Efficacy and safety of Ophiocordyceps sinensis in the treatment of Hashimoto's thyroiditis: a systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of Ophiocordyceps sinensis (OS) preparations for the treatment of Hashimoto's thyroiditis (HT). Methods: We searched eight databases to collect randomized controlled trials (RCTs) of OS combined with a low-iodine diet or levothyroxine for HT. The search period was from inception to June 2023. Meta-analysis was performed using Revman 5.3 software after two evaluators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. The GRADE system was used to assess the certainty of evidence. Results: A total of 14 RCTs involving 1,014 patients with HT were included. Meta-analysis showed that OS preparations combined with a low-iodine diet were more effective in reducing thyroid peroxidase antibody (TPOAb) [SMD = -3.81, 95% CI (-5.07, -2.54), p < 0.00001] and thyroglobulin antibody (TgAb) [SMD = -4.73, 95% CI (-6.86, -2.61), p < 0.00001] compared to a low-iodine diet. Compared with levothyroxine treatment alone, OS preparations combined with levothyroxine further reduced TPOAb [SMD = -2.04, 95% CI (-2.82, -1.26), p < 0.00001], TgAb [SMD = -2.01, 95% CI (-2.68, -1.33), p < 0.00001], tumor necrosis factor alpha (TNF-α) [SMD = -3.40, 95% CI (-5.66, -1.14), p = 0.003], interleukin-2 (IL-2) [SMD = -2.31, 95% CI (-3.98, -0.65), p = 0.006], and interleukin-6 (IL-6) [MD = -4.16, 95% CI (-6.17, -2.15), p < 0.0001], and elevated free thyroxine (FT4) [SMD = 1.34, 95% CI (0.59, 2.08), p = 0.0004], but no significant effect on free triiodothyronine (FT3) [SMD = 0.83, 95% CI (-0.12, 1.78), p = 0.09] and thyroid stimulating hormone (TSH) [SMD = -0.80, 95% CI (-1.71, 0.11), p = 0.08]. In terms of safety, three studies reported adverse reactions in 10 patients in each of the experimental and control groups. Conclusion: OS preparations in combination with other treatments (low-iodine diet or levothyroxine) may decrease thyroid autoantibodies and inflammatory responses in patients with HT. In HT patients with hypothyroidism, the combination of the OS preparations with levothyroxine also improved FT4. However, the quality of the included studies was generally low. Moreover, the safety of OS preparations remains unclear. Therefore, more high-quality, multicenter, large-sample RCTs are needed in the future to validate the efficacy and safety of OS preparations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023432663.

Epichloë endophytes improved Leymus chinensis tolerance to both neutral and alkali salt stresses.

Symbiotic relationships with microbes may influence how plants respond to environmental change. In the present study, we tested the hypothesis that symbiosis with the endophytes promoted salt tolerance of the native grass. In the field pot experiment we compared the performance of endophyte-infected (E+) and endophyte-uninfected (E-) Leymus chinensis, a dominant species native to the Inner Mongolia steppe, under altered neutral and alkaline salt stresses. The results showed that under both neutral and alkaline salt stresses, endophyte infection significantly increased plant height, leaf length and fibrous root biomass. Under neutral salt stress, endophyte infection decreased Na+ content and Na+/K+ ratio (p=0.066) in the leaf sheath while increased Ca2+ and Mg2+ content in the rhizome. Under alkali salt stress, endophyte infection tended to increase K+ content in the fibrous root, enhance Mg2+ content in the fibrous root while reduce Na+/K+ ratio in the leaf blade in the 100 mmol/L alkali salt treatment. Although endophyte-infected L. chinensis cannot accumulate Na+ high enough to be halophytes, the observed growth promotion and stress tolerance give endophyte/plant associations the potential to be a model for endophyte-assisted phytoremediation of saline-alkaline soils.

Effect of Addition of Thyroxine in the Treatment of Graves' Disease: A Systematic Review.

Graves' disease is the most common cause of hyperthyroidism. Antithyroid drugs, radioiodine ablation, and surgery are the main treatments. Research has demonstrated that adding thyroxine to antithyroid therapy can improve the remission rate, and many similar studies have been conducted subsequently. The purpose of this systematic review was to investigate whether adding thyroxine to various treatments for Graves' disease has a clinical benefit in remission/relapse rate, stable thyroid function, occurrence of Graves' ophthalmopathy, etc. A total of 27 studies were included, and the risk of research bias was moderate to high. We discuss the role of thyroxine both in pharmacological and non-pharmacological therapeutic regimens. Overall, the available evidence does not support the indiscriminate addition of thyroxine to various treatments for Graves' disease, especially in combination with oral antithyroid drugs. Further clinical studies are required to explore the indications of thyroxine addition in the treatment of Graves' disease.

Endophyte-mediated effects on the growth and physiology of Achnatherum sibiricum are conditional on both N and P availability.

The interaction of endophyte-grass associations are conditional on nitrogen (N) availability, but the reported responses of these associations to N are inconsistent. We hypothesized that this inconsistency is caused, at least in part, by phosphorus (P) availability. In this experiment, we compared the performance of endophyte-infected (EI) and endophyte-free (EF) Achnatherum sibiricum subjected to four treatments comprising a factorial combination of two levels of N (N+ vs. N-, i.e. N supply vs. N deficiency) and two levels of P (P+ vs. P-, i.e. P supply vs. P deficiency) availability. The results showed that A. sibiricum-Neotyphodium associations were conditional on both N and P availability, but more conditional on N than P. Under N+P- conditions, endophyte infection significantly improved acid phosphatase activity of EI plants, such that the biomass of EI plants was not affected by P deficiency (i.e. similar growth to N+P+ conditions), and resulted in more biomass in EI than EF plants. Under N-P+ conditions, biomass of both EI and EF decreased compared with N+P+; however, EI biomass decreased slowly by decreasing leaf N concentration more rapidly but allocating higher fractions of N to photosynthetic machinery compared with EF plants. This change of N allocation not only improved photosynthetic ability of EI plants but also significantly increased their biomass. Under N-P- conditions, EI plants allocated higher fractions of N to photosynthesis and had greater P concentrations in roots, but there was no significant difference in biomass between EI and EF plants. Our results support the hypothesis that endophyte-grass interactions are dependent on both N and P availability. However, we did not find a clear cost of endophyte infection in A. sibiricum.