The effects of ketogenic diet on brain gene expressions in type 2 diabetes background.

Type 2 diabetes mellitus (T2DM) is a major risk factor of a number of neurodegenerative diseases (NDDs). Ketogenic diet (KD) has significant beneficial effects on glycemic control and may act effectively against NDDs, but the mechanism remains unclear. In this study, we aimed to investigate the potential effects of KD on gene expressions in the brains of T2DM model mice. Male db/db mice at the age of 9 weeks were fed with KD or normal diet to the age of 6 months, and the whole brains were subjected to mRNA-seq analysis for differentially expressed genes. KD significantly lowered fasting glucose and body weights in db/db mice (P<0.05), and the expression of 189 genes in the brain were significantly changed (P<0.05, |log2|>1). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the differentially expressed genes upon KD are involved in inflammatory responses and the functions of biosynthesis. In inflammatory responses, NF-κB signaling pathway, viral protein interaction with cytokine and cytokine receptor, and cytokine-cytokine receptor interaction pathways were enriched, and in biosynthesis pathways, genes functioning in lipid and amino acid metabolism, protein synthesis, and energy metabolism were enriched. Moreover, consistent with the gene set enrichment analysis results, proteasomal activity measured biochemically were enhanced in KD-fed T2DM mice. These data may facilitate the understanding of how KD can be protective to the brain in T2DM background. KD could be a new strategy for the prevention of NDDs in T2DM patients.

Salicylic acid alleviates Zn-induced inhibition of growth via enhancing antioxidant system and glutathione metabolism in alfalfa.

Zinc (Zn) is considered as one of the heavy metal pollutants in soil affecting agriculture. Salicylic acid (SA) is an important phytohormone that can mitigate effects against various abiotic stresses in plants, however, its exploration to improve Zn stress tolerance in alfalfa plants is still elusive. Thus, in the present study, exogenous SA treatment was conducted on alfalfa plants under Zn stress. The effects of exogenous SA on the physiological effects of alfalfa plants and the expression levels related genes were studied. This study tested the biomass, relative water content, chlorophyll levels, photosynthetic capacity, proline and soluble sugar contents, detected the activity of antioxidant enzymes (such as peroxidase and superoxide dismutase), glutathione biosynthesis, and endogenous SA levels, and quantified the genes associated with the antioxidant system and glutathione metabolism-mediated Zn stress. The results showed that exogenous SA could elevate the physiological adaptability of alfalfa plants through enhancing photosynthesis, proline and soluble sugar levels, stimulating antioxidant system and glutathione metabolism, and inducing the transcription level of related genes, thereby diminishing oxidative stress, inhibiting excessive Zn accumulation of alfalfa plants, increasing tolerance to Zn stress, and reducing the toxicity of Zn. Collectively, the application of SA alleviates Zn toxicity in alfalfa plants. The findings gave first insights into the regulatory mechanism of the Zn stress tolerance of alfalfa by exogenous SA and this might have positive implications for managing other plants which are suffering Zn stress.

Association between body fat and sarcopenia in older adults with type 2 diabetes mellitus: A cross-sectional study.

Objectives: To investigate the association between body fat (BF%) and sarcopenia in older adults with type 2 diabetes mellitus (T2DM) and potential link with increased levels of inflammatory indicators and insulin resistance. Methods: A total of 543 older adults with T2DM were included in this cross-sectional study. Appendicular skeletal muscle (ASM), handgrip strength and gait speed were measured to diagnose sarcopenia according to the updated Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition data were tested using dual-energy X-ray absorptiometry (DEXA). Levels of serum high-sensitive C-reactive protein (hs-CRP), interleukin-6, fasting blood insulin (FINS), hemoglobin A1c (HbA1c), 25-hydroxyvitamin D3 [25(OH) D3] were also determined. Results: The prevalence of sarcopenia in all participants was 8.84%, of which 11.90% were male and 5.84% females. The Pearson's correlation analysis revealed that BF% was negatively correlated with gait speed in men and women (R =-0.195, P=0.001; R = -0.136, P =0.025, respectively). After adjusting for all potential confounders, sarcopenia was positive associated with BF% (male, OR: 1.38, 95% CI: 1.15-1.65, P< 0.001; female, OR: 1.30, 95% CI: 1.07-1.56, P=0.007), and negatively associated with body mass index (BMI) (male, OR: 0.57, 95% CI: 0.44-0.73, P<0.001; female, OR: 0.48, 95% CI: 0.33-0.70, P<0.001). No significant differences were found in hs-CRP, interleukin-6, and insulin resistance between older T2DM adults with and without sarcopenia. Conclusion: Higher BF% was linked to an increased risk of sarcopenia in older adults with T2DM, suggesting the importance of assessing BF% rather than BMI alone to manage sarcopenia.

Assessment of the impact of shift work on thyroid disorders: a systematic review and meta-analysis.

PURPOSE: Shift work including night work is a common work pattern worldwide and researchers have no consensus on the impact of shift work on thyroid disorders. We aimed to conduct a meta-analysis to summarize the evidence from published studies to ascertain the impact of shift work on thyroid disorders. METHODS: Studies on the link between shift work and thyroid disorders published in Pubmed, Embase, Medline, and Cochrane databases by September 2021 were searched. Newcastle-Ottawa scale was used to assess the quality of included studies. The Mantel-Haenszel statistical method and the inverse-variance statistical method were used to evaluate the pooled results of dichotomous and continuous variables, respectively. Study heterogeneity analysis was performed using I2 statistics. Sensitivity analysis was conducted by omitting one study each time and re-calculating the pooled results of the remaining studies. RESULTS: Seven eligible studies were included in the systematic review and meta-analysis. The results showed that shift work would lead to an increase in TSH (SMD: 0.30; 95%CI: 0.05-0.55; P = 0.02; I2 = 64%) and FT4 (SMD: 0.21; 95%CI: 0.02-0.40; P = 0.03; I2 = 0%). However, shift work had no clear effect on the risk of positive thyroid autoantibodies (OR: 1.26; 95%CI: 0.62-2.55; P = 0.52; I2 = 63%). CONCLUSION: Shift work may be associated with abnormal TSH and FT4 levels. Thyroid health is affected in shift workers and it is advisable to remind patients to get good sleep the night before testing thyroid function.

Effects of sleep deprivation on coronary heart disease.

The presence of artificial light enables humans to be active 24 h a day. Many people across the globe live in a social culture that encourages staying up late to meet the demands of various activities, such as work and school. Sleep deprivation (SD) is a severe health problem in modern society. Meanwhile, as with cardiometabolic disease, there was an obvious tendency that coronary heart disease (CHD) to become a global epidemic chronic disease. Specifically, SD can significantly increase the morbidity and mortality of CHD. However, the underlying mechanisms responsible for the effects of SD on CHD are multilayered and complex. Inflammatory response, lipid metabolism, oxidative stress, and endothelial function all contribute to cardiovascular lesions. In this review, the effects of SD on CHD development are summarized, and SD-related pathogenesis of coronary artery lesions is discussed. In general, early assessment of SD played a vital role in preventing the harmful consequences of CHD.

Chronic Sleep Deprivation Impaired Bone Formation in Growing Rats and Down-Regulated PI3K/AKT Signaling in Bone Tissues.

Background: This study aimed to assess the effects of chronic sleep deprivation (CSD) on bone metabolism in growing rats and the likely underlying mechanism. Methods: Twenty 5-week-old male Wistar rats and randomly divided into the CSD and normal control (NC) groups after one-week acclimatization. After a 6-week intervention of sleep deprivation, the distal femurs of both groups were harvested for micro-computed tomography scans and histological analysis. Meanwhile, the femur tissues were measured the mRNA and protein expression via RNA sequencing and immunohistochemical analysis. Serum bone turnover markers were evaluated at 0, 2, 4, and 6 weeks. Results: CSD impaired the bone growth, showing an imbalance of bone turnover status, dysphasia in the metaphysis growth plate, and deterioration of bone microarchitecture. Further, CSD suppressed bone formation, showing that the expression of osteogenesis-related proteins (col1α1 and osteocalcin) and mRNA (igf1, bglap, runx2, col1α1, pth1r) are down-regulated. Differentially expressed genes were detected, and functional enrichment analyses revealed that the PI3K/AKT pathway was significantly down-regulated in the CSD group. Conclusion: These results suggest that CSD can significantly impaire bone health, and it may exert these effects in part by suppressing bone formation and osteoblast differentiation, and inactivating the PI3K/AKT signaling pathway.

The GH-IGF-1 Axis in Circadian Rhythm.

Organisms have developed common behavioral and physiological adaptations to the influence of the day/night cycle. The CLOCK system forms an internal circadian rhythm in the suprachiasmatic nucleus (SCN) during light/dark input. The SCN may synchronize the growth hormone (GH) secretion rhythm with the dimming cycle through somatostatin neurons, and the change of the clock system may be related to the pulsatile release of GH. The GH-insulin-like growth factor 1 (IGF-1) axis and clock system may interact further on the metabolism through regulatory pathways in peripheral organs. We have summarized the current clinical and animal evidence on the interaction of clock systems with the GH-IGF-1 axis and discussed their effects on metabolism.

Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development.

The relationship between type 2 diabetes mellitus (T2DM) and pancreatic cancer (PC) is complex. Diabetes is a known risk factor for PC, and new-onset diabetes (NOD) could be an early manifestation of PC that may be facilitate the early diagnosis of PC. Metformin offers a clear benefit of inhibiting PC, whereas insulin therapy may increase the risk of PC development. No evidence has shown that novel hypoglycemic drugs help or prevent PC. In this review, the effects of T2DM on PC development are summarized, and novel strategies for the prevention and treatment of T2DM and PC are discussed.

Bone turnover markers are associated with the PTH levels in different subtypes of pseudohypoparathyroidism type 1 patients.

OBJECTIVE: Bone responsiveness to parathyroid hormone (PTH) in different subtypes of pseudohypoparathyroidism type 1 (PHP1) remains controversial. We aimed to investigate this phenomenon using bone turnover markers (BTMs) in a large cohort of PHP1 patients. DESIGN: Retrospective study. PATIENTS: Sixty-three PHP1 patients diagnosed by molecular analysis were used as subjects, and 48 sex- and age-matched patients with nonsurgical hypoparathyroidism (NS-HP) were used for comparison. MEASUREMENTS: Bone turnover markers, alkaline phosphatase (ALP), C-terminal telopeptide of type I collagen (ß-CTX) and related parameters in PHP1 were compared among different subtypes and with NS-HP. RESULTS: Among all the PHP1 patients (15 PHP1A, 14 familial 1B and 34 sporadic 1B), 23.8% had elevated baseline BTM levels. No significant difference was found in the ß-CTX levels among different subtypes. The ß-CTX level was positively correlated with the PTH level for all PHP1, PHP1B and PHP1A patients (B = 0.001, 0.001 and 0.004, respectively; all p < .05). The BTM levels of PHP1 patients were significantly higher than those of NS-HP patients (ß-CTX: 0.56 ng/ml vs. 0.20 ng/ml, p = .001; ALP: 105 U/L vs. 72 U/L, p = .001). The serum ß-CTX levels in different PHP1 subtypes were all significantly higher than those in NS-HP patients in adults. Among the 22 followed up patients, changes in BTMs were associated with changes in PTH (ß-CTX: r = .507, p = .023; ALP: r = .475, p = .034). CONCLUSIONS: Bone tissues respond to PTH in different PHP1 subtypes, and it is reasonable to monitor and normalize PTH and BTMs in addition to the serum and urinary calcium levels in the follow-up of PHP1 patients.

Application of new international classification of adult-onset diabetes in Chinese inpatients with diabetes mellitus.

BACKGROUND: To determine whether the new international cluster-based classification method can be applied to Chinese inpatients with diabetes mellitus (DM). METHODS: Adult patients with DM hospitalized in our tertiary care centre from January 2017 to December 2018 were included in the study. K-means cluster analysis was done in clusters based on glutamic acid decarboxylase antibodies, body mass index, glycosylated haemoglobin, homeostasis model-assessed beta cell function, insulin resistance index, and age at diagnosis of DM. Chi-square test was used to analyse inter-subgroup differences in DM-related complications and family history of DM. p < 0.05 was considered significant. RESULTS: A total of 1152 inpatients with DM were included in the study. Five subgroups were obtained by cluster analysis with highest proportion of population in mild obesity-related DM subgroup (34.55%), followed by mild age-related DM (21.55%), severe insulin deficiency DM (20.51%), severe insulin resistance DM (19.02%), and severe autoimmune DM subgroup (4.36%). The prevalence of diabetic retinopathy, diabetic peripheral vascular disease, diabetic ketosis, coronary heart disease, hypertension, and family history of DM differed significantly among the subgroups (p < 0.05 for all). CONCLUSIONS: This cluster-based classification could be applied to hospitalized adult patients with DM in China. It might help in strategizing for DM patients, and hence, improve management of DM in these patients.