Influence of lifestyle patterns on depression among adults with diabetes: a mediation effect of dietary inflammatory index.

BACKGROUND: Lifestyle has become a crucial modulator in the management of diabetes and is intimately linked with the development and exacerbation of comorbid depression. The study aimed to analyze lifestyle patterns and their impact on depression in individuals with diabetes and to explore the role of the Dietary Inflammatory Index (DII) in the relationship between lifestyle patterns and depression. METHODS: Data was attained from the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2020. A latent class analysis (LCA) was performed on 3,009 diabetic adults based on lifestyle behaviors. A generalised linear model (GLM) was employed to analyse the effects of different lifestyle patterns on depression. The mediation effect model was utilised to examine the relationship between lifestyle patterns, DII and Patient Health Questionnaire-9 (PHQ-9) scores. RESULTS: The cohort was divided through LCA into unhealthy lifestyle (44.53%), unhealthy but non-alcohol use (48.06%) and healthy but smoking (7.41%) groups of lifestyle behaviors, the unhealthy but non-alcohol use group was identified as a risk factor for depression (OR = 1.379, 95%CI = 1.095 ~ 1.735, P = 0.006). The DII partially mediated the relationship between the unhealthy but non-alcohol use group and PHQ-9, and fully mediated the relationship between the healthy but smoking group and PHQ-9, with effect coefficients of - 0.018 (95%CI: -0.044 ~ - 0.001) and - 0.035 (95%CI: -0.083 ~ - 0.001). CONCLUSIONS: Lifestyle patterns significantly influence the occurrence of depression among diabetes patients. The dietary inflammation plays a varying mediating role between different lifestyle patterns and depression. Restricting pro-inflammatory diets or encouraging anti-inflammatory diets, combined with the promotion of healthy lifestyle practices, may be an effective method for preventing and alleviating symptoms of depression among patients with diabetes.

Raspberry Ketone Prevents LPS-Induced Depression-Like Behaviors in Mice by Inhibiting TLR-4/NF-κB Signaling Pathway via the Gut-Brain Axis.

SCOPE: Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food-derived phenolics. Raspberries, renowned globally for their delectable flavor, harbor a phenolic compound known as raspberry ketone (RK). However, the impact of RK on depressive symptoms remains ambiguous. This study aims to investigate the impact of RK on lipopolysaccharide (LPS)-induced depressed mice and elucidates its potential mechanisms, focusing on the gut-brain axis. METHODS AND RESULTS: Through behavioral tests, RK exerts a notable preventive effect on LPS-induced depression-like behaviors in mice. RK proves capable of attenuating gut inflammation, repairing gut barrier impairment, modulating the composition of the gut microbiome (Muribaculaceae, Streptococcus, Lachnospiraceae, and Akkermansia), and promoting the production of short-chain fatty acids. Furthermore, RK alleviates neuroinflammation by suppressing the TLR-4/NF-κB pathway and bolsters synaptic function by elevating levels of neurotrophic factors and synapse-associated proteins. CONCLUSION: The current study provides compelling evidence that RK effectively inhibits the TLR-4/NF-κB pathway via the gut-brain axis, leading to the improvement of LPS-induced depression-like behaviors in mice. This study addresses the research gap in understanding the antidepressant effects of RK and illuminates the potential of utilizing RK as a functional food for preventing depression.

Distribution of lean mass and mortality risk in patients with type 2 diabetes.

AIMS: The aim of the study is to evaluate the association of distribution of lean mass with the risk of all-cause mortality among patients with type 2 diabetes. METHODS: The present cohort study included 2 335 patients with type 2 diabetes. Lean mass was assessed by dual energy X-ray absorptiometry. Cox proportional hazards regressions were used to estimate the association of lean mass distribution on the risk of mortality. RESULTS: The average age of the patients was 58 years at baseline and 51.4% of patients were women. During a median follow-up of 4.31 years, 128 patients died. The multivariable-adjusted hazards ratios for all-cause mortality were 1.00, 1.63 (0.89-2.99), and 2.68(1.51-4.76) across the tertiles of android-to-gynoid lean mass ratio (P for trend < 0.001), respectively. The positive association of android-to-gynoid lean mass ratio with the risk of all-cause mortality was present among patients of different ages, body mass index ≥ 24 kg/m2, hemoglobin A1c ≥ 7.0%, nonsmokers, men, patients using insulin, and patients with diabetes durations of more than 10 years. CONCLUSIONS: Higher android-to-gynoid lean mass ratio, assessed by dual energy X-ray absorptiometry, was significantly associated with increased risk of all-cause mortality among patients with type 2 diabetes.

Different roles of the RAAS affect bone metabolism in patients with primary aldosteronism, Gitelman syndrome and Bartter syndrome.

BACKGROUND: Components of the RAAS may influence bone metabolism. Different roles of the RAAS are found in patients with primary aldosteronism (PA), Gitelman syndrome (GS) and Bartter syndrome (BS). We collected inpatient medical records including 20 patients with Gitelman syndrome (GS group), 17 patients with Bartter syndrome (BS group) and 20 age-matched patients with primary aldosteronism (PA group). We found the following results. (1) PA patients had significantly higher serum magnesium, potassium, plasma aldosterone, serum parathyroid hormone, urinary calcium and BMI (p<0.05) while significantly lower serum calcium and phosphorus (P < 0.05) than GS and BS patients. (2) Total hip and femoral neck bone mineral density (BMD) in PA patients were significantly lower than those in GS and BS patients (P<0.05). (3) GS patients had lower serum magnesium and urinary calcium than BS patients (P < 0.05). (4) Compared with BS patients, the vertebral BMD in GS patients were significantly higher (P < 0.05). So we believe higher aldosterone and PTH levels may be the reason that PA patients have lower hip BMD. Lower urinary calcium and inactivation of the NCC gene (Na-Cl cotransporter) in GS patients may have protective effects on vertebral bone mineral density. CONCLUSIONS: With persistence disordered RAAS, PA patients have lower BMD, especially hip BMD as compared with GS and BS patients. We presumed the lower renin and higher aldosterone level may be the reason. With the same level of renin and aldosterone, BS patients have lower vertebrate BMD than GS patients. Decreased urinary calcium excretion may be the reason.

Different Indicators of Adiposity and Fat Distribution and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes.

OBJECTIVE: This study aimed to evaluate the effect of adiposity and fat distribution on the odds of elevated cardiovascular risk factors among adults with type 2 diabetes mellitus. METHODS: The present cross-sectional study included 2,427 adults with type 2 diabetes mellitus. Body fat was assessed by dual-energy x-ray absorptiometry. Multivariate-adjusted logistic regression was used to estimate effects of adiposity parameters on elevated hemoglobin A1c (HbA1c , ≥7.0%), hypertension (blood pressure ≥140/90 mmHg), and elevated low-density lipoprotein (LDL) cholesterol (≥2.6 mmol/L). RESULTS: The multivariable-adjusted odds ratio (OR) for elevated HbA1c was 0.82 (95% CI: 0.70-0.96) for each SD increase in leg fat mass. The multivariable-adjusted OR for hypertension was 1.15 (95% CI: 1.00-1.32) for each SD increase in android fat mass. Multivariable-adjusted ORs for elevated LDL cholesterol ranged from 1.16 (95% CI: 1.00-1.35) to 1.27 (95% CI: 1.06-1.51) for each SD increase in arm and android fat mass and percentage of total, truncal, arm, and android fat. Each SD increase in BMI, truncal-to-leg fat ratio, and android-to-gynoid fat ratio was significantly associated with increased risks of elevated HbA1c , hypertension, and elevated LDL cholesterol. CONCLUSIONS: Subcutaneous fat in the lower body was associated with a more favorable glycemic profile, but not blood pressure or lipid profile, whereas central adiposity was associated with poor control of cardiovascular risk factors among patients with type 2 diabetes mellitus.

Evaluating distal renal tubular acidification function in primary hyperparathyroidism and its effects on bone mineral density.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrinopathy that may increase fracture risk and decrease bone mineral density (BMD). Some patients develop distal renal tubular acidification dysfunction under conditions of hyperchloraemia or hyperchloraemic acidosis. To examine whether this dysfunction influences the clinical outcome, we explored the distal renal tubular acidification function in patients with PHPT and its effects on the clinical manifestations of the disease. METHODS: We retrospectively analysed 75 PHPT patients with regard to renal tubular acidification and blood gas analysis. The patients were divided into two groups, the renal tubular acidification dysfunction group and normal function group. RESULTS: Serum phosphate level and total hip bone density were significantly decreased and 25OHD level was significantly increased in the renal tubular acidification dysfunction group in comparison to the normal function group. Female patients in the renal tubular acidification dysfunction group showed significantly decreased femoral neck and total hip BMD and increased susceptibility to fracture. However, there were no such differences in male patients between the two groups. CONCLUSIONS: About 54.6 % of PHPT patients in our study population had abnormal distal renal tubular acidification. PHPT patients with abnormal distal renal tubular acidification may have lower hip bone density. Female PHPT patients with abnormal distal renal tubular acidification showed increased susceptibility to fractures and the development of osteoporosis.

Iron as electron donor for denitrification: The efficiency, toxicity and mechanism.

For the treatment of low C/N wastewaters, methanol or acetate is usually dosed as electron donor for denitrification but such organics makes the process costly. To decrease the cost, iron which is the fourth most abundant element in lithosphere is suggested as the substitution of methanol and acetate. The peak volumetric removal rate (VRR) of nitrate nitrogen in the ferrous iron-dependent nitrate removal (FeNiR) reactor was 0.70 ± 0.04 kg-N/(m3·d), and the corresponding removal efficiency was 98%. Iron showed toxicity to cells by decreasing the live cell amount (dropped 56%) and the live cell activity (dropped 70%). The toxicity of iron was mainly expressed by the formation of iron encrustation. From microbial community data analysis, heterotrophs (Paracocccus, Thauera and Azoarcus) faded away while the facultative chemolithotrophs (Hyphomicrobium and Anaerolineaceae_uncultured) dominated in the reactor after replacing acetate with ferrous iron in the influent. Through scanning electron microscope (SEM) and transmission electron microscope (TEM), two iron oxidation sites in FeNiR cells were observed and accordingly two FeNiR mechanisms were proposed: 1) extracellular FeNiR in which ferrous iron was bio-oxidized extracellularly; and 2) intracellular FeNiR in which ferrous iron was chemically oxidized in periplasm. Bio-oxidation (extracellular FeNiR) and chemical oxidation (intracellular FeNiR) of ferrous iron coexisted in FeNiR reactor, but the former one predominated. Comparing with the control group without electron donor in the influent, FeNiR reactor showed 2 times higher and stable nitrate removal rate, suggesting iron could be used as electron donor for denitrification. However, further research works are still needed for the practical application of FeNiR in wastewater treatment.

Selective inhibition of progesterone receptor in osteochondral progenitor cells, but not in mature chondrocytes, modulated subchondral bone structures.

OBJECTIVE: The presence or relative proportion of progesterone nuclear receptors (PR) in different tissues may contribute to sexual dimorphism in these tissues. PR is expressed in chondrocytes, but its function is mostly unknown. We hypothesized that the PR may regulate chondrocyte metabolism and affect subchondral bone structure. METHODS: We utilized genetic fate mapping and immunohistochemistry to elucidate PR expression in and effect on cartilage. To define sex-dependent and chondrocyte-specific effects of the PR on subchondral bone, we selectively deleted PR in osteochondrogenic progenitor cells marked by Prx1 (Prx1; PRcKO) and Collagen 2 (Col2; PRcKO), or in matured chondrocytes marked by aggrecan (Acan; PRcKO) and evaluated subchondral bone structure at 4 months of age. Chondrocyte aging was monitored by anti-senescence marker p16INK4a, and MMP13, one of the Senescence-Associated Secretary Phenotype (SASP) components. RESULTS: Compared to wild-type (WT) mice, the female Prx1; PRcKO and the Col2; PRcKO mice had greater total subchondral bone volume and greater subchondral cortical bone thickness, with increased estimated subchondral bone stiffness and failure load in both female and male Col2; PRcKO mice. Moreover, Col2; PRcKO mice from both sexes had greater bone formation and bone strength at the femurs. In contrast, we did not observe any subchondral bone changes in Acan; PRcKO mice other than higher work-to-failure observed in the male Acan; PRcKO mice. Despite no detected difference in articular cartilage between the WT and the PR; chondrocyte conditional deletion mice, there were greater numbers of senescent chondrocytes and increased MMP13 expression, especially in the male mutant mice. CONCLUSION: These findings suggest that selective inhibition of PR in osteoprogenitor cells, but not in terminally differentiated chondrocytes, induced an increased subchondral bone phenotype and high estimated subchondral bone strength, which might be associated with the development of osteoarthritis in older age.

Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing's disease.

Objective To investigate the effects of Cushing's disease (CD) and adrenal-dependent Cushing's syndrome (ACS) on bone mineral density (BMD) and bone metabolism. Methods Data were retrospectively collected for 55 patients with hypercortisolism (CD, n = 34; ACS n = 21) from January 1997 to June 2014. BMD was examined in all patients, and bone turnover markers were tested in some patients. Healthy controls (n = 18) were also recruited. Results The lumbar spine and femoral neck BMD were significantly lower in the ACS and CD groups than in the control group. Lumbar BMD was significantly lower in the ACS than CD group. The collagen breakdown product (CTX) concentrations were significantly higher while the osteocalcin and procollagen type I N-terminal propeptide (PINP) concentrations were significantly lower in the ACS and CD groups than in the control group. The PINP concentration was significantly lower while the CTX concentration was significantly higher in the ACS than CD group. In the CD group only, lumbar BMD and serum adrenocorticotropic hormone had a significant positive correlation. Conclusions Bone turnover markers indicated suppressed osteoblast and enhanced osteoclast activities. PINP and CTX changes might indicate bone mass deterioration. Adrenocorticotropic hormone might be protective for lumbar BMD in patients with CD.

Oxidative decomposition properties of cationic exchange resins producing SO4(2-) in power plants.

The sulphate content of a system increases when strong-acid cationic exchange resins leak into a system or when sulphonic acid groups on the resin organic chain detach. To solve this problem, a dynamic cycle method was used in dissolution experiments of several resins under H2O2 or residual chlorine conditions. Results show that after performing dynamic cycle experiments for 120 hours under oxidizing environments, the SO4(2-) and total organic carbon (TOC) released by four kinds of resins increased with time, contrary to their release velocity. The quantity of released SO4(2-) increased as the oxidizing ability of oxidants was enhanced. Results showed that the quantity and velocity of released SO4(2-) under residual chlorine condition were larger than those under H2O2 condition. Data analysis of SO4(2-) and TOC released from the four kinds of resins by the dynamic cycle experiment revealed that the strength of oxidation resistance of the four resins were as follows: 650C>1500H>S200>SP112H.

Parathyroid hormone-related protein regulates osteoclast inhibitory lectin expression via multiple signaling pathways in osteoblast-like cells.

Osteoclast inhibitory lectin (OCIL) is a recently identified inhibitor of osteoclast formation. A variety of osteotropic factors regulate OCIL expression in osteoblastic cells, however, little information is available to date concerning how this gene is controlled. Using real-time RT-PCR, we examined the regulation of OCIL expression by PTHrp and the signaling pathways used. We demonstrated in rat osteoblast-like UMR-106 cells, rat calvarial primary osteoblastic cells, and murine MC3T3-E1 cells, PTHrp(1-34) increased OCIL expression. In UMR-106 cells, the increase began and reached maximum later than RANKL induction and OPG suppression. cAMP/PKA signaling activators PTH(1-31), forskolin and dibutyryl cAMP (db-cAMP), and calcium ionophore A23187 all increased OCIL levels. In contrast, PKC activator phorbol-12-myristate-13-acetate reduced OCIL expression in short term but induced OCIL mRNA in long term. PKA inhibitor KT5720, mitogen-activated protein kinase (MAPK) cascade inhibitor PD98059, calmodulin antagonist W-7, and Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) inhibitor KN-62 all significantly blunted PTHrp-stimulated OCIL expression. Moreover, PD98059 blocked the stimulation of OCIL by FSK or db-cAMP but not that by A23187. In primarily cultured osteoblasts, the PTHrp induction of OCIL was blocked by KT5720, W-7, and PD98059 as well. The data established that PTHrp(1-34) regulates OCIL expression in vitro through cAMP/PKA, Ca(2+)/CaMK II, and MAPK signaling pathways.

Recombinant soluble receptor activator of nuclear factor-kappaB inhibits parathyroid hormone-induced osteoclastogenesis in vitro.

The recent identification of receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) cytokine system has led to a new molecular perspective on osteoclast biology and bone homeostasis. Specifically, the interaction between RANKL and RANK is responsible for osteoclast differentiation. In the present study, we evaluated whether soluble RANK (sRANK) could act as an antagonist of RANKL and down-regulate osteoclastogenesis and bone resorption in vitro. The prokaryotic expression vector coding for sRANK was constructed. Then the construct was introduced into E. coli Origami B (DE3) competent cells and recombinant sRANK was successfully produced and purified through affinity chromatography. sRANK reduced osteoclast-like cell (OLC) formation and resorption pit formation induced by parathyroid hormone (PTH) in a dose-dependent manner. In addition, sRANK significantly inhibited PTH-induced mRNA expression of carbonic anhydrase II and tartrate-resistant acid phosphatase in murine bone marrow cells as confirmed by using semi-quantitative RT-PCR. The down-regulation was highly correlated with the effect of sRANK on OLC formation from marrow cells. These data demonstrate the anti-resorptive effects of sRANK in vitro and highlight the potential of sRANK as a novel therapeutic approach to bone disorders characterized by enhanced bone resorption.

Construction of a restriction-endonuclease-Eam1105I-generated T-vector for high-throughput cloning and expression.

A novel T-vector was constructed that could be used for direct cloning and expression of PCR-amplified cDNA. The technique was based on the insertion into the parent vector of two endonuclease-Eam1105I restriction sequences spaced by an expression cassette of the full-length beta-galactosidase, which helped to improve cloning efficiency and to minimize the non-recombinant background of the T-vector when used to clone PCR products. Moreover, this method took advantage of the reconstitution of the rarest restriction sequence of MssI to enable directional cloning. These advantages make the T-vector suitable for high-throughput expression and analysis.

[Impacts of osteoclast-like cells cultured on bone wafer and their sub-cellular structures on osteoblast].

OBJECTIVE: To investigate the effects of osteoclast-like cells (OLC) and its sub-cellular structures on the osteoblast (OB) differentiation and function. METHODS: Spleen cells from C57 mice administrated with 5-fluorouracil were induced by IL-3, 6 and granulocyte-macrophage colony stimulating factor (GM-CSF), and 1alpha, 25-(OH)(2)D(3) to obtain massive OLCs. These OLC cells were cultured in culture fluid and on bone wafers (called bolcs). Osteoblasts were cultured and added with NaF, OLCs of two kinds, culture fluid free of OLC, and sub-unit structures such as nucleus, mitochondria, and cytoplasma from OLCs for 5 days. The proliferation rate of OBs was measured by MTT method and the alkaline phophatase (ALP) activity was measured by PNPP method. Immunochemistry was used to detect the core-binding factor alpha1 (Cbfalpha1) in the OBs, Enzyme linked immunosorbent assay was used to measure the osteocalcin. RESULTS: The OB number was lower in the OLC (1.288 +/- 0.039), OLC cytoplasm (1.138 +/- 0.024), 50% OLC culture fluid (1.203 +/- 0.033), 50% OLC culture medium of OLCs cultured on bone wafer (1.128 +/- 0.028) in comparison with the pure OB group (1.393 +/- 0.016, all P < 0.05). The increase functions of OBs by OLC cultured on bone wafer and their nucleus and mitochondria were all more significant than those of the OLCs not cultured on bone wafer. The ALP activity was increased in the NaF (1.027 +/- 0.024), OCL cytoplasm (1.850 +/- 0.033), 50% OLC medium (2.074 +/- 0.065), 50% OLC medium of OLCs cultured on bone wafer (1.718 +/- 0.048), and mitochondria and cytoplasm of the OLC cultured on bone wafer groups (1.246 +/- 0.037, all P < 0.05). NaF (0.0825 +/- 0.0025), OLCs (0.0775 +/- 0.0025), nucleus (0.0775 +/- 0.0025), mitochondria (0.0875 +/- 0.0025), and cytoplasm of OLCs (0.1100 +/- 0.0007), 50% OLC medium (0.0900 +/- 0.0000), 50% OLC medium of OLCs cultured on bone wafer (0.1200 +/- 0.0041), OLCs cultured on bone wafer and nucleus, mitochondria, and cytoplasm of OLCs cultured on bone wafer all significantly increase the oeteocalcin activity of OBs (0.525 +/- 0.0063, all P < 0.05). NaF (57.6% +/- 2.6%), OLC cytoplasm (45.3% +/- 4.7%), 50% OLC medium (46.6% +/- 3.3%), 50% medium of OLCs cultured on bone wafer (54.0% +/- 2.1%), OLCs cultured on bone wafer (44.8% +/- 3.0%), and cytoplasm of OLCs cultured on bone wafer (48.7% +/- 3.5%) all significantly increased the Cbfalpha1 protein in the OBs (32.8% +/- 4.5%, all P < 0.05). CONCLUSION: The sub-cellular elements of OLC and the supernatant of OLC culture media free of OLC promote the functions of OB, especially the OLCs cultured on bone wafer.

[Distribution of tetracycline-arginine-glycine-aspartate-tyrosine in mice and its effect on bone].

OBJECTIVE: To investigate the distribution of tetracycline-arginine-glycine-aspartate-tyrosine (T-RGDY) in mice and its effect on bone. METHODS: 125-labeled T-RGDY was studied for its distribution in mice and for its effects on bone by histomorphometry in ovariectomized rats. RESULTS: The 125I-labeled T-RGDY was more concentrated in the osteoporotic bone than in the normal bone. Compared with ovariectomy group, the morphologic index such as trabecular bone volume/total tissue volume (TBV/TTV), TBV/sponge bone volume (SBV), and mean trabecular plate thickness (MTPT) in T-RGDY group significantly increased (P < 0.05). As compared with sham operation group, MTPT significantly increased in T-RGDY group (P < 0.05), while TBV/SBV and mean trabecular plate density significantly decreased (P < 0.05), and TBV/TYV and mean trabecular plate spacing were almost the same as those in sham operation group (P > 0.05). CONCLUSION: T-RGDY may concentrate in bone tissue to a certain degree, which is closely related with the status of bone remodeling. T-RGDY may inhibit the bone loss caused by ovariectomy.