Schlank orchestrates insect developmental transition by switching H3K27 acetylation to trimethylation in the prothoracic gland.

Insect developmental transitions are precisely coordinated by ecdysone and juvenile hormone (JH). We previously revealed that accumulated H3K27 trimethylation (H3K27me3) at the locus encoding JH signal transducer Hairy is involved in the larval-pupal transition in insects, but the underlying mechanism remains to be fully defined. Here, we show in Drosophila and Bombyx that Rpd3-mediated H3K27 deacetylation in the prothoracic gland during the last larval instar promotes ecdysone biosynthesis and the larval-pupal transition by enabling H3K27me3 accumulation at the Hairy locus to induce its transcriptional repression. Importantly, we find that the homeodomain transcription factor Schlank acts to switch active H3K27 acetylation (H3K27ac) to repressive H3K27me3 at the Hairy locus by directly binding to the Hairy promoter and then recruiting the histone deacetylase Rpd3 and the histone methyltransferase PRC2 component Su(z)12 through physical interactions. Moreover, Schlank inhibits Hairy transcription to facilitate the larval-pupal transition, and the Schlank signaling cascade is suppressed by JH but regulated in a positive feedback manner by ecdysone. Together, our data uncover that Schlank mediates epigenetic reprogramming of H3K27 modifications in hormone actions during insect developmental transition.

Fzr regulates silk gland growth by promoting endoreplication and protein synthesis in the silkworm.

Silkworm silk gland cells undergo endoreplicating cycle and rapid growth during the larval period, and synthesize massive silk proteins for silk production. In this study, we demonstrated that a binary transgenic CRISPR/Cas9 approach-mediated Fzr mutation in silkworm posterior silk gland (PSG) cells caused an arrest of silk gland growth and a decrease in silk production. Mechanistically, PSG-specific Fzr mutation blocked endoreplication progression by inducing an expression dysregulation of several cyclin proteins and DNA replication-related regulators. Moreover, based on label-free quantitative proteome analysis, we showed in PSG cells that Fzr mutation-induced decrease in the levels of cyclin proteins and silk proteins was likely due to an inhibition of the ribosome biogenesis pathway associated with mRNA translation, and/or an enhance of the ubiquitin-mediated protein degradation pathway. Rbin-1 inhibitor-mediated blocking of ribosomal biogenesis pathway decreased DNA replication in PSG cells and silk production. Altogether, our results reveal that Fzr positively regulates PSG growth and silk production in silkworm by promoting endoreplication and protein synthesis in PSG cells.

Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomes.

Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs). Neuronal p53 transactivated the promoter of microRNA-183 (miR-183) cluster, thereby upregulating biogenesis of miR-183-5p (miR-183), miR-96-5p (miR-96), and miR-182-5p. Both miR-183 and miR-96 directly targeted and post-transcriptionally suppressed VDACs. Neuronal ablation of p53 protected against ATP deficiency and neurological deficits, whereas post-stroke rescue of miR-183/VDAC signaling reversed these benefits. Interestingly, cyclin-dependent kinase 9 (CDK9) was found to be enriched in cortical neurons and upregulated the p53-induced transcription of the miR-183 cluster in neurons after ischemia. Post-treatment with the CDK9 inhibitor oroxylin A promoted neuronal ATP production mainly through suppressing the miR-183 cluster/VDAC axis, further improved long-term sensorimotor abilities and spatial memory, and alleviated depressive-like behaviors in mice following stroke. Our findings reveal an intrinsic CDK9/p53/VDAC pathway that drives neuronal bioenergy decline and underlies post-stroke cognitive impairment and depression, thus highlighting the therapeutic potential of oroxylin A for better outcomes.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

Long-Chain Lipids Facilitate Insertion of Large Nanoparticles into Membranes of Small Unilamellar Vesicles.

Insertion of hydrophobic nanoparticles into phospholipid bilayers is limited to small particles that can incorporate into a hydrophobic membrane core between two lipid leaflets. Incorporation of nanoparticles above this size limit requires the development of challenging surface engineering methodologies. In principle, increasing the long-chain lipid component in the lipid mixture should facilitate incorporation of larger nanoparticles. Here, we explore the effect of incorporating very long phospholipids (C24:1) into small unilamellar vesicles on the membrane insertion efficiency of hydrophobic nanoparticles that are 5-11 nm in diameter. To this end, we improve an existing vesicle preparation protocol and utilized cryogenic electron microscopy imaging to examine the mode of interaction and evaluate the insertion efficiency of membrane-inserted nanoparticles. We also perform classical coarse-grained molecular dynamics simulations to identify changes in lipid membrane structural properties that may increase insertion efficiency. Our results indicate that long-chain lipids increase the insertion efficiency by preferentially accumulating near membrane-inserted nanoparticles to reduce the thermodynamically unfavorable disruption of the membrane.

Costunolide alleviates atherosclerosis in high-fat diet-fed ApoE-/- mice through covalently binding to IKKß and inhibiting NF-κB-mediated inflammation.

Costunolide (CTD) is a sesquiterpene lactone isolated from costus root and exhibits various biological activities including anti-inflammation. Since atherosclerosis is a chronic inflammatory disease, we herein investigated the anti-atherosclerotic effects of CTD and the underlying mechanism. Atherosclerosis was induced in ApoE-/- mice by feeding them with a high-fat diet (HFD) for 8 weeks, followed by administration of CTD (10, 20 mg ·kg-1·d-1, i.g.) for 8 weeks. We showed that CTD administration dose-dependently alleviated atherosclerosis in HFD-fed ApoE-/- mice. Furthermore, we found that CTD dose-dependently reduced inflammatory responses in aortas of the mice, as CTD prevented infiltration of inflammatory cells in aortas and attenuated oxLDL uptake in macrophages, leading to reduced expression of pro-inflammatory and pro-fibrotic molecules in aortas. Similar results were observed in oxLDL-stimulated mouse primary peritoneal macrophages (MPMs) in vitro. We showed that pretreatment with CTD (2.5, 5. 10 µM) restrained oxLDL-induced inflammatory responses in MPMs by blocking pro-inflammatory NF-κB/p65 signaling pathway. We further demonstrated that CTD inactivated NF-κB via covalent binding to cysteine 179 on IKKß, a canonical upstream regulator of NF-κB, reducing its phosphorylation and leading to conformational change in the active loop of IKKß. Our results discover IKKß as the target of CTD for its anti-inflammatory activity and elucidate a molecular mechanism underlying the anti-atherosclerosis effect of CTD. CTD is a potentially therapeutic candidate for retarding inflammatory atherosclerotic diseases.

Cerebral Gray Matter Volume Changes in Patients with Neuropathic Pain from Total Brachial Plexus Injury.

INTRODUCTION: Total brachial plexus injury not only significantly affects the motor and sensory function of the affected upper limbs but also causes further physical and mental damage to patients with long-term intractable pain. Previous studies mainly focused on the surgical treatment, while only a few paid attention to the intractable neuropathic pain caused by this injury. Changes in the volume of gray matter in the brain are thought to be associated with chronic neuropathic pain. METHODS: Voxel-based morphometry analysis was used to compare the difference in cerebral gray matter volume between total brachial plexus injury patients with neuropathic pain and healthy controls. Correlations between pain duration, pain severity, and GM changes were analyzed. RESULTS: The volume of cerebral gray matter in the patient group was decreased significantly in multiple regions, including the parahippocampal gyrus, paracentric lobule, inferior frontal gyrus, auxiliary motor cortex, middle occipital gyrus, right middle temporal gyrus, while it was increased in the insular, pons, middle frontal gyrus, cingulate gyrus, inferior parietal lobule, bilateral thalamus, and globus pallidus. There were no significant correlations between pain duration and rGMV changes, while a positive correlation was observed between pain severity and rGMV changes in one specific region, involving the anterior cingulate cortex. CONCLUSION: Total brachial plexus injury patients with chronic pain have widespread regions of gray matter atrophy and hypertrophy. The only positive correlation was observed between pain severity and rGMV changes in one specific region, suggesting that nociceptive stimuli trigger a variety of nonpain-specific processes, which confirms the multidimensional nature of pain.

Retardation of Myopia by Multifocal Soft Contact Lens and Orthokeratology: A 1-Year Randomized Clinical Trial.

OBJECTIVES: This randomized, single-blind, clinical trial compared the effectiveness of multifocal soft contact lenses (MFSCLs), orthokeratology contact lenses (Ortho-kCLs), and single vision spectacles (SVSs) for myopia control. METHODS: Sixty-six eligible Chinese subjects, aged 7 to 15 years old with cycloplegic refraction measurements between -1.00 and -8.00 diopters (D), astigmatism not more than 1.00 D, and no history of myopia control treatment, were randomly assigned to wear MFSCLs, Ortho-kCLs, or SVSs for 1 year. For all three groups, baseline measurements of cycloplegic refraction, axial length (AL), and corneal endothelial cell density (CECD) were made. At the 6- and 12-month follow-up visits, changes in cycloplegic refraction, AL, and CECD were measured in the MFSCL and SVS groups. For the Ortho-kCL group, only changes in the AL were measured at 6 and 12 months, and CECD was measured at the 12-month follow-up visit. RESULTS: After 1 year of lens wear, myopia progression of the SVS group, -0.938±0.117 D, was greater than that of the MFSCLs group, -0.591±0.106 D (P=0.032). Thus, MFSCLs reduced the rate of myopia progression by 37.0% compared with the SVSs. The AL elongations after 1 year were 0.30±0.03 mm for MFSCLs (P=0.027 vs SVSs), 0.31±0.04 mm for Ortho-kCLs (P=0.049 vs SVSs), and 0.41±0.04 mm for SVSs. Compared with the SVS group, the reduction in AL elongation was 26.8% and 24.4% in the MFSCL and Ortho-kCL groups, respectively. There were no significant differences in CECD among the three groups (P>0.05). CONCLUSIONS: Compared with SVSs, wearing MFSCLs and Ortho-kCLs significantly delayed myopia progression. MFSCLs and Ortho-kCLs are safe and promising methods of myopia control (chictr.org number, ChiCTR2100048452).

Pharmacokinetics and tissue distribution study of obtusifolin in rats by liquid chromatography-tandem mass spectrometry.

This paper reports the validation of an assay for obtusifolin based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application to a preclinical pharmacokinetic study in rats. After sample preparation of plasma and tissue homogenates by protein precipitation, the analyte and internal standard (IS) were separated by a reversed-phase chromatographic system in a run time of 5.0 min and detected by negative ion electrospray ionization followed by selected reaction monitoring of the precursor-to-product ion transitions at m/z 283.0-268.1 for obtusifolin and m/z 329.0-314.1 for IS. The assay was linear in the concentration range 1.0-500 ng/ml with the LLOQ of 1.0 ng/ml. In the pharmacokinetic study of an intragastric administration of 1.3 mg/kg obtusifolin, the maximum plasma concentration of obtusifolin was 152.5 ± 62.3 ng/ml, reached at 0.39 ± 0.17 h. The AUC0-t and AUC0-∞ were 491.8 ± 256.7 and 501.7 ± 256.7 ng × h/ml, respectively, with an elimination half-life of 3.1 ± 0.7 h. Obtusifolin was rapidly distributed into tissues, with the highest distribution in the liver and less in the brain. These results will give some insights for further pharmacological investigation of obtusifolin.

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway.

Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodium-taurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP.

Dolabellane and Clerodane Diterpenoids from the Twigs and Leaves of Casearia kurzii.

A pair of enantiomeric 15-nordolabellane diterpenoids, (-)- and (+)-caseadolabellols A (1a and 1b), three dolabellane diterpenoids, caseadolabellols B-D (2-4), two dolastane diterpenoids, caseadolastols A and B (5 and 6), 10 clerodane diterpenoids, caseakurzins A-J (7-16), and nine known diterpenoids (17-25) were isolated from the twigs and leaves of Casearia kurzii. The structures of the new compounds were established on the basis of extensive spectroscopic data, and those of compounds 1a, 1b, and 2 were verified by single-crystal X-ray crystallographic analysis. The enantiomers 1a and 1b were separated by chiral-phase HPLC. The absolute configurations were determined by experimental and calculated ECD data, the modified Mosher's method, or literature comparison. Compounds 1a and 5 showed significant quinone reductase-inducing activity in Hepa 1c1c7 cells, while 1b showed moderate activity. Molecular docking studies showed that 1a had greater binding affinity with Nrf2 protein (5FNQ) than 1b. The cytotoxic activity of compounds 1a, 1b, 2-12, 15, and 16 was evaluated, among which compounds 8 and 16 exhibited significant inhibitory activity against the A549 cell line. Compounds 8 and 16 induced the A549 cells to arrest at G2/M and S phases, respectively, and both compounds induced apoptosis in A549 cells.

Mm9_circ_009056 enhances osteogenesis by targeting BMP7 via CGRP-mediated miR-22-3p.

Circular RNAs (circRNAs) are noncoding RNAs that can function as miRNA sponges, post-transcriptionally regulating the expression of genes. Here, we report a novel positive function of mm9_circ_009056 during osteogenesis in regulating bone morphogenetic protein 7 (BMP7) through miR-22-3p. First, we found that calcitonin gene-related peptide (CGRP) had great osteogenesis function on MC3T3 cells. Then aberrant expression of mm9_circ_009056 were confirmed in CGRP-induced cells. Furthermore, the expression of mm9_circ_009056 was up-regulated in the CGRP-induced cells, whereas miR-22-3p was obviously decreased. Silencing of mm9_circ_009056 increased the expression of miR-22-3p and decreased the gene and protein levels of BMP7, RUNX2. Cells proliferation and growth were also inhibited following silengcing. The protein levels of BMP7 and RUNX2 decreased after mimics transfection and increased after inhibitors transfection. In summary, mm9_circ_009056 may function as a sponge for miR-22-3p to regulate osteogenesis in CGRP-induced cells.

Cellular prion protein is involved in decidualization of mouse uterus.

Prion protein (PrP) is encoded by a single copy gene Prnp in many cell and tissue types. PrP is very famous for its infectious conformers (PrPSC) resulting in transmissible spongiform encephalopathies. At present, physiological functions of its cellular isoform (PrPC) remain ambiguous. Although PrPC expression has been found in uterus, whether it functions in maternal-fetal dialogue during early pregnant is unknown. In this study, we examined PrPC mRNA and protein in the uterus of peri-implantation mice, and found that they were expressed with a spatiotemporal dynamic pattern. Interestingly, PrPC was significantly increased in the decidual zones around the implanting embryos at the implantation window stage. To further demonstrate that PrPC is involved in the decidualization of mouse uterus during embryo implantation, we constructed the artificial decidualization models and the delayed implantation models. Once the pseudopregnant mice were artificially induced to decidualization, the PrPC expression then increased significantly in the decidua zone. And also, if the delayed implantation embryos were allowed to implant, PrPC protein was also simultaneously improved in stromal cells surrounding the implanting embryos. Moreover, PrPC expression can be inhibited by progesterone but upregulated by estrogen in mouse uterus. These results suggest that PrPC may play an important role in embryo implantation and decidualization.

Microscopic and Submicroscopic Gradient Variation of Olfactory Systems among Six Sinocyclocheilus Species Living in Different Environments.

The fish genus Sinocyclocheilus contains many different species that inhabit diverse natural environments, such as surface water layer, cave, or intermediate. As a result of these different habitats there are some differences in their sensory systems. Microscopic and submicroscopic structures of olfactory systems in six representative species of Sinocyclocheilus were studied, including one surface-dwelling species (S. grahami), two intermediate species (S. jii and S. macrophthalmus) and three cave-dwelling species (S. brevibarbatus, S. anshuiensis, and S. tianlinensis). Due to adaptive evolution under extreme environmental conditions, cave-dwelling species have more developed olfactory systems. We observed that, compared with surface-dwelling species, the olfactory sac of the cave-dwelling Sinocyclocheilus species has the following characteristics: higher density of cilia, greater length of sensory cilia, many other special structures (micro-ridge, olfactory islet, rod cilia). These results reveal different levels of olfactory system development, consistent with the view that that cave-dwelling species have more developed olfactory systems than intermediate and surface-dwelling species.

Accumulation of methylglyoxal increases the advanced glycation end-product levels in DRG and contributes to lumbar disk herniation-induced persistent pain.

Lumbar disk herniation (LDH) with discogenic low back pain and sciatica is a common and complicated musculoskeletal disorder. The underlying mechanisms are poorly understood, and there are no effective therapies for LDH-induced pain. In the present study, we found that the patients who suffered from LDH-induced pain had elevated plasma methylglyoxal (MG) levels. In rats, implantation of autologous nucleus pulposus (NP) to the left lumbar 5 spinal nerve root, which mimicked LDH, induced mechanical allodynia, increased MG level in plasma and dorsal root ganglion (DRG), and enhanced the excitability of small DRG neurons (<30 µm in diameter). Intrathecal injection of MG also induced mechanical allodynia, and its application to DRG neurons ex vivo increased the number of action potentials evoked by depolarizing current pulses. Furthermore, inhibition of MG accumulation by aminoguanidine attenuated the enhanced excitability of small DRG neurons and the mechanical allodynia induced by NP implantation. In addition, NP implantation increased levels of advanced glycation end products (AGEs) in DRG, and intrathecal injection of MG-derived AGEs induced the mechanical allodynia and DRG neuronal hyperactivity. Intrathecal injection of MG also significantly increased the expression of AGEs in DRG. Importantly, scavenging of MG by aminoguanidine also attenuated the increase in AGEs induced by NP implantation. These results suggested that LDH-induced MG accumulation contributed to persistent pain by increasing AGE levels. Thus generation of AGEs from MG may represent a target for treatment of LDH-induced pain.NEW & NOTEWORTHY Our study demonstrates that methylglyoxal accumulation via increasing advanced glycation end-product levels in dorsal root ganglion contributes to the persistent pain induced by lumbar disk herniation, which proposed potential targets for the treatment of lumbar disk herniation-induced persistent pain.

The Role of Exogenous Hydrogen Sulfide in Free Fatty Acids Induced Inflammation in Macrophages.

BACKGROUND: This study aimed to investigate whether exogenous hydrogen sulfide (H2S) can protect the RAW264.7 macrophages against the inflammation induced by free fatty acids (FFA) by blunting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. METHODS: RAW264.7 macrophages were exposed to increasing concentrations of FFA for up to 3 days to induce FFA-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to FFA. Cell viability, cell apoptosis, TLR4, NF-κB, NLRP3 inflammasome, IL-1ß, IL-18 and cleaved caspase-3 expression were measured by a combination of MTT assay, ELISA, and immunoblotting. RESULTS: H2S attenuated FFA-induced cell apoptosis, and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL- 1ß, IL-18 and caspase-3. In addition, H2S inhibited the FFA-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. CONCLUSION: The present study demonstrated for the first time that H2S appears to suppress FFA-induced macrophage inflammation and apoptosis by inhibiting the TLR4/ NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H2S might possess potential in the treatment of diseases resulting from FFA overload like insulin resistance and type diabetes.

Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study.

Exercise training can reduce hepatic fat accumulation and cardiovascular risk among patients with non-alcoholic fatty liver disease (NAFLD), but how long these benefits extend beyond the period of active intervention is unclear. Intrahepatic triglyceride (IHTG) content, measured by proton magnetic resonance spectroscopy, and metabolic risk factors among 220 obese people with NAFLD, who were randomly assigned to vigorous/moderate exercise, moderate exercise or no exercise (control), were assessed at 1 year after the 12-month exercise intervention. IHTG content was significantly reduced in the 2 exercise groups compared with the control group over the 12-month active intervention. It was significantly lower (by -2.39%) in the vigorous/moderate exercise group compared with the control group at the 1-year follow-up (95% confidence interval -4.72 to -0.05%; P = .045). Waist circumference and blood pressure remained significantly lower in the vigorous/moderate exercise group and the moderate exercise group compared with the control group at the 1-year follow-up. Visceral adipose fat remained significantly reduced, but with no differences among 3 groups. These findings suggest 12-month exercise intervention induced reductions in hepatic fat accumulation, abdominal obesity and blood pressure for up to 1 year after the active intervention, with some attenuation of the benefits.

Sham Feeding with Chewing Gum in Early Stage of Acute Pancreatitis: A Randomized Clinical Trial.

BACKGROUND The correlation between sham feeding and acute pancreatitis (AP) has only been examined in limited studies. We aimed to investigate the efficacy and safety of sham feeding in the early stage of AP. MATERIAL AND METHODS A randomized controlled clinical trial was performed. Equal groups of AP patients were recruited. Patients in the sham feeding group received chewing gum 4 times a day after admission. All patients in the trial received standard treatment consistent with the guidelines for AP. The primary outcomes were mortality, length of stay (LOS), and medical expenses. Secondary outcomes were the incidence of complications and other adverse events, return of gastrointestinal function, the details of enteral nutrition and intra-abdominal pressure. RESULTS From May 2014 to December 2015, a total of 204 patients were recruited. The LOS and hospital costs in the sham feeding group were reduced, although mortality was equivalent between groups. The return of gastrointestinal function occurred earlier in the sham feeding group, with no complications related to gum chewing. CONCLUSIONS Sham feeding with chewing gum is safe and efficacious in the early stage of AP.

Associations of polymorphisms in TXNIP and gene-environment interactions with the risk of coronary artery disease in a Chinese Han population.

Single nucleotide polymorphisms (SNPs) in thioredoxin-interacting protein (TXNIP) gene may modulate TXNIP expression, then increase the risk of coronary artery disease (CAD). In a two-stage case-control study with a total of 1818 CAD patients and 1963 controls, we genotyped three SNPs in TXNIP and found that the variant genotypes of SNPs rs7212 [odds ratio (OR) = 1.26, P = 0.001] and rs7211 (OR = 1.23, P = 0.005) were significantly associated with increased CAD risk under a dominant model. In haplotype analyses, compared with the reference haplotype, haplotype 'G-T' had a 1.22-fold increased risk of CAD (P = 0.003). We also observed the cumulative effects of SNPs rs7212 and rs7211 on CAD risk and the severity of coronary atherosclerosis. Moreover, the gene-environment interactions among the variant genotypes of SNP rs7212, smoking habit, alcohol drinking habit and history of type 2 diabetes were associated with a 3.70-fold increased risk of CAD (P < 0.001). Subsequent genotype-phenotype correlation analyses further observed the significant effects of SNP rs7212 on TXNIP mRNA expression, plasma TXNIP and malondialdehyde levels. Taken together, our data suggest that TXNIP SNPs may individually and cumulatively affect CAD risk through a possible mechanism for regulating TXNIP expression and gene-environment interactions.

Outcome benefit of abdominal paracentesis drainage for severe acute pancreatitis patients with serum triglyceride elevation by decreasing serum lipid metabolites.

BACKGROUND: Our previous reports demonstrated that abdominal paracentesis drainage (APD) exerts a beneficial effect on severe acute pancreatitis (SAP) patients. However, the underlying mechanisms for this effectiveness are not well understood. METHODS: A retrospective cohort of 132 consecutive non-hypertriglyceridemia (HTG)-induced SAP patients with triglyceride (TG) elevation and pancreatitis-associated ascitic fluid (PAAF) was recruited from May 2010 to May 2015 and included in this study. The patients were divided into two groups: the APD group (n = 68) and the non-APD group (n = 64). The monitored parameters mainly included mortality, hospital stay, the incidence of further intervention, levels of serum lipid metabolites and inflammatory factors, parameters related to organ failure and infections, and severity scores. RESULTS: The demographic data and severity scores were comparable between the two groups. Compared with the non-APD group, the primary outcomes (including mortality, hospital stay and the incidence of percutaneous catheter drainage) in the APD group were improved. The serum levels of lipid metabolites were significantly lower in the APD group after 2 weeks of treatment than in the non-APD group. Logistic regression analysis indicated that the decreased extent of free fatty acid (FFA)(odds ratio, 1.435; P = 0.015) was a predictor of clinical improvement after 2 weeks of treatment. CONCLUSION: Treatment with APD benefits non-HTG-induced SAP patients with serum TG elevation by decreasing serum levels of FFA.