A distinct role of STING in regulating glucose homeostasis through insulin sensitivity and insulin secretion.

Insulin resistance and ß-cell dysfunction are two main molecular bases yet to be further elucidated for type 2 diabetes (T2D). Accumulating evidence indicates that stimulator of interferon genes (STING) plays an important role in regulating insulin sensitivity. However, its function in ß-cells remains unknown. Herein, using global STING knockout (STING-/-) and ß-cell-specific STING knockout (STING-ßKO) mouse models, we revealed a distinct role of STING in the regulation of glucose homeostasis through peripheral tissues and ß-cells. Specially, although STING-/- beneficially alleviated insulin resistance and glucose intolerance induced by high-fat diet, it surprisingly impaired islet glucose-stimulated insulin secretion (GSIS). Importantly, STING is decreased in islets of db/db mice and patients with T2D, suggesting a possible role of STING in ß-cell dysfunction. Indeed, STING-ßKO caused glucose intolerance due to impaired GSIS, indicating that STING is required for normal ß-cell function. Islet transcriptome analysis showed that STING deficiency decreased expression of ß-cell function-related genes, including Glut2, Kcnj11, and Abcc8, contributing to impaired GSIS. Mechanistically, the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and cleavage under targets and tagmentation (CUT&Tag) analyses suggested that Pax6 was the transcription factor that might be associated with defective GSIS in STING-ßKO mice. Indeed, Pax6 messenger RNA and protein levels were down-regulated and its nuclear localization was lost in STING-ßKO ß-cells. Together, these data revealed a function of STING in the regulation of insulin secretion and established pathophysiological significance of fine-tuned STING within ß-cells and insulin target tissues for maintaining glucose homeostasis.

Bufalin inhibits the malignant development of non-small cell lung cancer by mediating the circ_0046264/miR-522-3p axis.

BACKGROUND: Bufalin is an active component of the traditional Chinese medicine "Chan Su" and is reported to play anti-tumor roles in cancer development, but its functional mechanism is largely unclear. This study intends to explore a potential action mode of bufalin in NSCLC. MATERIALS AND METHODS: The malignant properties of NSCLC, including cell viability, proliferation, adhesion capacity, migration and invasion, were monitored by cell counting kit-8 (CCK-8), adhesion assay and transwell assay, respectively. The expression of circ_0046264 and miR-522-3p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of proliferation- and migration-related markers was examined by western blot. The putative relationship between circ_0046264 and miR-522-3p was verified by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Animal experiments in nude mice were performed to investigate the role of bufalin in vivo. RESULTS: Bufalin treatment inhibited cell viability, colony formation, cell adhesion capacity, migration and invasion in NSCLC cells. Bufalin facilitated the expression of circ_0046264, and circ_0046264 overexpression also inhibited NSCLC cell viability, colony formation, cell adhesion capacity, migration and invasion. Besides, circ_0046264 knockdown partially counteracted the effects of bufalin. Further, miR-522-3p was identified as a target of circ_0046264, and its deficiency reversed the effects of circ_0046264 knockdown to suppress malignant activities of NSCLC cells. In addition, bufalin restrained the tumor growth and development in vivo via enhancing the expression of circ_0046264. CONCLUSION: Bufalin played an anti-tumor role in NSCLC by modulating the circ_0046264/miR-522-3p pathway, which might be a potential functional mechanism of bufalin in NSCLC.

Urinary iodine in early pregnancy is associated with subclinical hypothyroidism in Tianjin, China: an observational study.

BACKGROUND: Subclinical hypothyroidism (SH) is associated with adverse obstetric outcomes and neurodevelopment disorders. Both iodine deficiency and excess are associated with SH; however, few data regarding iodine nutrition status of pregnant women with SH are available. This study aimed to clarify whether iodine deficiency or excess is associated with SH, especially, when test results for anti-thyroid autoantibodies are negative. METHODS: A total of 115 women with SH and 104 women with euthyroidism (EH) in early pregnancy in Tianjin, China were investigated, and their serum thyroid-stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroid peroxidase antibody (TPOAb), anti-thyroid globulin antibody (TGAb), urinary iodine (UIC), and urinary creatinine (UCr) concentrations were measured. Thyroid ultrasonography was performed to determine thyroid echogenicity and volume. The UIC, UIC/UCr ratio, prevalence of TPOAb and TGAb positivity, and thyroid gland volume were compared between the EH and SH groups. UIC and ultrasonographic features were analysed in subjects in the SH group who were negative for TPOAb and TGAb. RESULTS: Median UIC of SH (154.0 µg/L) and EH (150.1 µg/L) met the World Health Organization criterion for iodine sufficiency in pregnant women. Neither UIC nor the UIC/UCr ratio differed significantly between groups. The prevalence of TPOAb and TGAb positivity in the SH group was significantly higher than that in the EH group (P < 0.01). The percentage of subjects with UIC ≥ 250 µg/L in the SH group was significantly higher than that in the EH group (p = 0.004). The percentage of subjects negative for autoantibodies and UIC ≥ 250 µg/L in the SH group tended to be higher than that in subjects in the EH group negative for autoantibodies, but the difference was not statistically significant (p = 0.025, adjusted test level α = 0.0167). Eight of 18 subjects in the SH group with negative results for TPOAb and TGAb were diagnosed with Hashimoto thyroiditis by means of thyroid ultrasonography. CONCLUSIONS: Women in early pregnancy with SH in Tianjin were iodine sufficient, but still at risk of iodine deficiency as pregnancy progressed. UIC ≥ 250 µg/L was associated with increased risk of SH. Serological negative autoimmune thyroiditis and UIC ≥ 250 µg/L may play a role in pathogenesis of SH cases with negative results for autoantibodies.

Hyperguanyes A and B, two new PPAPs from the branches and leaves of Hypericum perforatum L. with anti-cholinesterase activities.

Two new polycyclic polyprenylated acylphloroglucinols, hyperguanyes A and B (1-2) together with eight known compounds (3-10), were isolated from Hypericum perforatum L. Their structures were determined by using comprehensive spectroscopic techniques and quantum chemical calculation. The in vitro anti-cholinesterase activity of all compounds were studied. Among them, compounds 1-4, 8 and 9 exhibited anti-AchE and anti-BchE effects with IC50 ranging from 0.34 ± 0.04 to 15.68 ± 0.54 µM.

Effects of different sowing dates on biomass allocation of various organs and allometric growth of Fagopyrum esculentum.

Introduction: The sowing date plays a crucial role in influencing the growth and reproduction of plants, with its specific impact on biomass allocation and allometric growth remaining unclear. Understanding these effects is essential for optimizing agricultural practices and enhancing crop productivity. Methods: To investigate the effects of sowing dates on biomass allocation and allometric growth, a field experiment was conducted with sequential sowings of Fagopyrum esculentum from April 12th to August 11th in 2018. Biomass measurements were taken across various plant organs, and corresponding allocation calculations were made. A detailed analysis of the allometric growth relationship involving organ biomass variations was performed. Results: The study revealed that the accumulation and allocation of organ biomass in buckwheat were significantly impacted by the sowing dates. Delayed planting led to reduced vegetative growth and increased biomass allocation towards reproduction. Allometric parameters such as exponent, constant, and individual size of buckwheat were notably affected by delayed planting. Interestingly, the allometric exponents governing the relationships between reproductive vs. vegetative biomass and belowground vs. aboveground biomass exhibited varying trends across different sowing dates. Discussion: Notably, late sowings resulted in significantly higher reproductive biomass compared to early and middle sowings. These findings highlight the nuanced relationship between plant size and reproductive biomass under different sowing dates, emphasizing the critical role of planting timing in shaping mature plant sizes and reproductive outcomes. The study underscores the importance of considering sowing dates in agricultural practices to optimize plant growth and productivity.

Boosting supercapacitor performance of carbon fibres using electrochemically reduced graphene oxide additives.

Modifying conventional materials with new recipes represents a straightforward yet efficient way to realize large-scale applications of new materials. Electrochemically reduced graphene oxide (ERGO) coated carbon fibres (CFs), prepared as fibre-like supercapacitor electrodes, exhibited excellent electrochemical energy storage performance. Upon addition of only a small amount (~1 wt%) of ERGO, the hybrid fibres showed superior electrochemical capacitances (nearly three orders of magnitude enhanced) compared to pure CFs in both aqueous and gel electrolytes. Meanwhile, the energy density did not decrease notably as the power density increased. The superior capacitive performance could be attributed to the synergistic effect between wrinkled and porous ERGO sheets and highly conductive CFs. This fibre electrode material also offered advantages such as easy operation, mass production capability, mechanical flexibility and robustness, and could have an impact on a wide variety of potential applications in energy and electronic fields.

Hyperipersions A-C, three new acylphloroglucinols from the branches and leaves of Hypericum perforatum L. with antiangiogenic activities.

Three new acylphloroglucinols were isolated from the branches and leaves of Hypericum perforatum L., named as hyperipersions A-C (1-3), together with three known compounds which were identified as elegaphenone (4), 2,6-dihydroxy-3,4-dimethylbenzoic acid methyl ester (5) and 2,3-methylenedioxyxanthone (6), respectively. The structures of isolated compounds were determined by UV, IR, HR-ESI-MS, NMR analysis. Their antiangiogenic activities were studied against HUVECs. The IC50 value of compound 3 was 2.39 ± 0.21 µM against HUVECs, which was stronger than vatalanib, and other compounds had moderate antiangiogenic activity.

Association between TyG index and long-term mortality of critically ill patients: a retrospective study based on the MIMIC Database.

OBJECTIVE: To evaluate the association of triglyceride-glucose (TyG) index on admission with outcomes of critically ill patients. DESIGN: A retrospective study. SETTING: A population-based cohort study of Medical Information Mart for Intensive Care III Database (MIMIC III). PARTICIPANTS: All intensive care unit admissions were extracted from MIMIC III. MAIN OUTCOME MEASURES: The TyG index was calculated as ln [triglycerides (mg/dL)×glucose (mg/dL)/2]. The primary endpoint was 360-day mortality. RESULTS: A total of 3902 patients with an average age of 63.1±15.9 years old were enrolled, including 1623 (41.6%) women. The 360-day mortality was lower in a higher TyG group. Compared with the lowest TyG group, the HR of 360-day mortality was 0.79 (95% CI (0.66, 0.95); p=0.011) in the fully adjusted Cox model and 0.71 (95% CI (0.59, 0.85); p<0.001) in the stepwise Cox model. In the subgroup analysis, an interaction effect was detected between TyG index and gender. CONCLUSIONS: A lower TyG index was associated with the risk of 360-day mortality in critically ill patients, which could be a predictor of long-term survival of critically ill patients.

Comparison of cardiorenal safety of nonsteroidal anti-inflammatory drugs in the treatment of arthritis: a network meta-analysis.

Background: Arthritis includes osteoarthritis (OA), rheumatoid arthritis (RA), and other arthritis-related disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used drugs for the treatment of arthritis. However, there remains a concern that some currently used NSAIDs may increase the risk of cardiorenal adverse events in patients with arthritis. Although it has been established that some NSAIDs are associated with a higher risk of cardiovascular and renal events, their safety varies widely. To provide insight into drug use, this study systematically assessed and compared the incidence of cardiovascular and renal events in different NSAIDs by using Bayesian meta-analysis. Methods: The PubMed, Cochrane Library, and Embase databases were searched for randomized controlled trials (RCTs) on NSAIDs. Databases were searched from the inception to April 25, 2022. Two investigators independently screened articles according to the Population, Intervention, Comparator, Outcomes, Study design (PICOS) principle, extracted data, and assessed the quality of articles using Cochrane Risk of Bias assessing tools. R software (version 4.1.3) was used for network meta-analysis (NMA). Results: The analysis ultimately included 20 articles with a total of 144,957 patients and 13 interventions. The risk of bias in the included articles was generally moderate. Ibuprofen was associated with the highest incidence of hypertension outcomes [comparing with placebo OR (95% CI): 3.24 (1.71, 5.82)], rofecoxib with the highest incidence of renal events [comparing with placebo OR (95% CI): 4.46 (1.49, 14.73)], ibuprofen with the highest incidence of cardiovascular events [comparing with placebo OR (95% CI): 2.39 (0.82, 8.06), and naproxen with the highest incidence of edema [comparing with placebo OR (95% CI): 2.31 (1.16, 4.47)]. Conclusions: The NMA results showed that amtolmetin guacil was relatively safer, but it needs further investigation. Rofecoxib was associated with a higher incidence of cardiorenal adverse events, ibuprofen with a higher incidence of cardiovascular events and hypertension, and naproxen with a higher incidence of renal events and edema. Clinicians should weigh the efficacy of NSAIDs against renal and cardiovascular toxicity when prescribing NSAIDs for the treatment of arthritis.

Low Serum Dehydroepiandrosterone Is Associated With Diabetic Kidney Disease in Men With Type 2 Diabetes Mellitus.

Background: The associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with diabetic kidney disease (DKD) remained unclear. Thus, this cross-sectional study aimed to explore the associations of DHEA and DHEAS with the risk of DKD in patients with T2DM. Methods: The information of 1251 patients with T2DM were included in this study. Serum DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry assays. Multivariate logistic regression analyses were used to assess the associations of DHEA and DHEAS with DKD as well as high urine albumin to creatinine ratio (ACR). Results: In men with T2DM, the risk of DKD decreased with an increasing DHEA concentration after adjustment for traditional risk factors; the fully adjusted OR (95% CI) for tertile3 vs tertile1 was 0.37 (0.19-0.70; P = 0.010 for trend). Similarly, when taking high ACR as the outcome, low DHEA levels were still significantly associated with increased odds of high ACR (OR, 0.37; 95% CI, 0.19-0.72 for tertile3 vs tertile1; P = 0.012 for trend). The restricted cubic spline showed that the risk of DKD gradually decreased with the increment of serum DHEA levels (P-overall = 0.007; P-nonlinear = 0.161). DHEAS was not independently associated with the risk of DKD in men. In contrast, no significant relationships were found between DHEA and DHEAS and the risk of DKD in women (all P > 0.05). Conclusions: In men with T2DM, low serum DHEA levels were independently related to the risk of DKD after adjustment for traditional risk factors. Our finding highlights the potential role of DHEA in the development of DKD in men with T2DM.

Fatty acid synthase (Fasn) inhibits the expression levels of immune response genes via alteration of alternative splicing in islet cells.

BACKGROUND: Increasing evidence has shown that fatty acid synthase (Fasn) is associated with diabetes mellitus (DM) and insulin resistance, however, it remains unclear how Fasn upregulation leads to dysregulation of energy homeostasis in islet cells. Consequently, uncovering the function of Fasn in islet cells. Consequently, uncovering the function of FASN in islet cells is immensely important for finding a treatment target. AIM: In this study, we elucidated the biological function of Fasn on the target genes in a rat insulinoma INS-1 cell line. METHODS: We created a Fasn overexpressing rat insulinoma cell line (Fasn-OE), and performed bulk RNA-sequencing (RNA-seq) experiments on Fasn-OE and INS-1 (control) cells. We first identified differentially expressed genes (DEGs) using Bioconductor package edgeR, and then discovered enriched gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the KEGG Orthology Based Annotation System (KOBAS) 2.0 web server. Furthermore, we identified alternative splicing events (ASEs) and regulated alternative splicing events (RASEs) by applying the ABLas pipeline. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for validation of selected differentially expressed genes (DEGs) and Fasn-regulated alternative splicing genes (RASGs). RESULTS: In this study we found that Fasn overexpression led to significant changes of gene expression profiles, including downregulations of mRNA levels of immune related genes, including Bst2, Ddit3, Isg15, Mx2, Oas1a, Oasl, and RT1-S3 in INS-1 cell line. Furthermore, Fasn positively regulated the expression of transcription factors such as Fat1 and Ncl diabetes-related genes. Importantly, Fasn overexpression to result in alternative splicing events including in a metabolism-associated ATP binding protein mRNA Abcc5. In Gene Ontology analysis, the downregulated genes in Fasn-OE cells were mainly enriched in inflammatory response and innate immune response. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the downregulated genes were mainly enriched in TNF signaling pathway and cytokine-mediated signaling pathways. CONCLUSIONS: Our findings showed that upregulation of Fasn may play a critical role in islet cell immunmetabolism via modifications of immune/inflammatory related genes on transcription and alternative splicing level, which provide novel insights into characterizing the function of Fasn in islet cell immunity and for the development of chemo/immune therapies.

An intron mutation of HNF1A causes abnormal splicing and impairs its activity as a transcription factor.

Mutations in HNF1A are associated with Maturity Onset Diabetes of the Young type 3 (MODY3) and most of them are in the coding region. Herein, we identified an intron mutation at the 6th nucleotide upstream of the end of intron 7 of HNF1A, named IVS7-6G > A, in a patient with early-onset diabetes. The "minigene" assay showed that IVS7-6G > A produced two aberrant mRNA variants translating into two truncated proteins: L502S fs* and G437A fs*, both affecting HNF1A transactivation domain (TAD). To determine functional consequences of IVS7-6G > A mutation, we made plasmids encoding truncated HNF1A containing different portions of HNF1A TAD and found that the TAD of HNF1A is important not only for its regulatory activities, but also for its nuclearization, and the residues 282-501 was more essential than 502-631. Our data suggested IVS7-6G > A impaired HNF1A splicing and may contribute to the pathogenesis of MODY3.

Vitamin D deficiency is associated with thyroid autoimmunity: results from an epidemiological survey in Tianjin, China.

PURPOSE: The pathogenesis of Hashimoto's thyroiditis (HT) is unclear, although some studies have identified an association between vitamin D deficiency and thyroid autoantibody positivity. This study aimed to investigate vitamin D status, and its relationships with thyroid autoantibody positivity and HT, via a large epidemiological survey. METHODS: The epidemiological survey was conducted in Tianjin, China. All participants underwent testing for serum 25-hydroxyvitamin D (25OHD), thyroid function, and thyroid autoantibodies, and some participants underwent testing to evaluate CD4+ T-cell differentiation and concentrations of related cytokines. RESULTS: The study included 1812 participants and revealed prevalences of 13.1% for thyroid peroxidase antibodies (i-TPOAb) and 14.0% for thyroglobulin antibodies (i-TgAb). Logistic regression analysis revealed that thyroid autoantibody positivity was associated with sex, age, and 25OHD classification. An increased likelihood of i-TPOAb positivity was associated with 25OHD deficiency (odds ratio [OR]: 2.428, 95% confidence interval [CI]: 1.383-4.261) and 25OHD inadequacy (OR: 1.198, 95% CO: 0.828-1.733; p = 0.008). An increased likelihood of i-TgAb positivity was associated with 25OHD deficiency (OR: 2.366, 95% CI: 1.366-4.099) and 25OHD inadequacy (OR: 1.263, 95% CI: 0.883-1.807; p = 0.009). Relative to healthy subjects, patients with HT had significantly higher proportions of Th1 and Th17 cells, as well as higher concentrations of related cytokines. CONCLUSIONS: This study revealed that vitamin D deficiency was associated with thyroid autoantibody positivity, and that vitamin D deficiency seems to be involved in the pathological mechanism underlying HT. Large randomized controlled trials are needed to investigate the effects of vitamin D supplementation on HT.

High prevalence of vitamin D deficiency and influencing factors among urban and rural residents in Tianjin, China.

There was a high prevalence of vitamin D deficiency among residents in Tianjin, China, especially among female residents, rural young adults, and elderly individuals. This is the first large-scale study evaluating vitamin D status in Tianjin, China, and we believe that it makes a significant contribution to the literature. PURPOSE: Vitamin D deficiency has been documented as a worldwide public health problem. To our knowledge, there has not been any large-scale study on vitamin D status in Tianjin, China. The aim of this study was to investigate vitamin D status among Tianjin residents and to determine influencing factors. METHODS: This is a community-based study, and residents from both urban and rural areas of Tianjin were enrolled. Each participant completed a questionnaire regarding basic characteristics and lifestyle information. Serum 25-hydroxyvitamin D [25(OH)D] levels were statistically analyzed according to sex, age, and region. Other factors associated with vitamin D deficiency were also explored. RESULTS: A total of 1814 participants were included, with mean serum 25(OH)D level of 49.44 ± 14.9 nmol/L; only 47.63% achieved the optimal (50-125 nmol/L) 25(OH)D level. Serum 25(OH)D levels were higher among male participants than among female participants (53.44 ± 13.94 versus 46.55 ± 14.91 nmol/L, P < 0.05) and among urban participants than among rural participants (50.4 ± 16.32 versus 48.65 ± 13.58 nmol/L, P < 0.05). Serum 25(OH)D levels were significantly higher among the age group of 40-49 years (50.7 ± 17.99 nmol/L) than among the ≥ 70 years (48.45 ± 14.49 nmol/L) or 18-29 years (47.81 ± 13.08 nmol/L) age groups. CONCLUSIONS: There was a high prevalence of vitamin D deficiency/inadequacy among Tianjin residents, especially among female participants, rural young adults, and elderly individuals. Vitamin D supplementation is imperative for these high-risk vitamin D-deficient residents.

Investigation on the factors that influence the prevalence of thyroid nodules in adults in Tianjin, China.

Studies have shown that prevalence of thyroid nodules (TNs) has been increasing recently. However, the factors that may influence TN prevalence is not fully understood. In this study, we aimed to understand the prevalence of TNs and identify possible factors that are associated with the prevalence of TNs in Tianjin, China. Subjects aged 18 years or older were randomly collected and all subjects received thyroid ultrasonography, physical examination and questionnaires. Subjects (n = 2647) were divided into the case group in which the subjects had TNs and the control group in which the subjects did not have TNs. Potential influencing factors on TNs including sex, age, iodine status, thyroid volume, thyroid hormone (TSH), thyroid autoantibody TPOAb, TGAb and living habits were analyzed. Our results showed that the overall TN prevalence was 26.7%. The prevalence of TNs in women was higher than that in men (P < 0.05). TN prevalence increased with age (P < 0.001), and a U-shaped curve relationship between urine iodine concentrations (UICs) and prevalence of TNs was observed. The positive rate of TPOAb and goiter rate in case group was higher than that in control group (P < 0.05). The thyroid volume in case group was larger than that in control group (P < 0.001). Other factors that may influence TNs included high blood pressure, iodized salt, menopause, seafood intake, and education levels. None of UIC, TSH, TPOAb and TGAb were associated with TN prevalence in regression models. In conclusion, our results showed that TNs prevalence in Tianjin was high. TNs prevalence was higher in women than in men, and it increases with age. The older, female, high education level physical labor and goiter are independent risk factors for TNs.

Severely low serum magnesium is associated with increased risks of positive anti-thyroglobulin antibody and hypothyroidism: A cross-sectional study.

Trace elements, such as iodine and selenium, are closely related to autoimmune thyroiditis and thyroid function. Low serum magnesium is associated with several chronic diseases; however, its associations with autoimmune thyroiditis and thyroid function are unclear. We investigated the relationships between low serum magnesium, autoimmune thyroiditis, and thyroid function in 1,257 Chinese participants. Demographic data were collected via questionnaires, and levels of serum thyroid stimulating hormone, anti-thyroid peroxidase antibody, anti-thyroglobulin antibody (TGAb), free thyroxine, serum magnesium, serum iodine, and urinary iodine concentration were measured. Participants were divided into serum magnesium level quartiles (≤0.55, 0.551-0.85, 0.851-1.15, and >1.15 mmol/L). The median serum magnesium level was 0.89 (0.73-1.06) mmol/L; levels ≤0.55 mmol/L were considered severely low (5.9% of participants). The risks of TGAb positivity and Hashimoto thyroiditis (HT) diagnosed using ultrasonography in the lowest quartile group were higher than those in the adequate magnesium group (0.851-1.15 mmol/L) (p < 0.01, odds ratios [ORs] = 2.748-3.236). The risks of total and subclinical-only hypothyroidism in the lowest quartile group were higher than those in the adequate magnesium group (0.851-1.15 mmol/L) (p < 0.01, ORs = 4.482-4.971). Severely low serum magnesium levels are associated with an increased rate of TGAb positivity, HT, and hypothyroidism.

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.