Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Jiangu granule ameliorated OVX rats bone loss by modulating gut microbiota-SCFAs-Treg/Th17 axis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a common disease that has decreased bone strength as its main symptom after menopause. Effective treatment for PMOP remains lacking, but traditional Chinese medicine has some advantages in delaying bone loss. Jiangu granule is a traditional Chinese medicine prescription commonly used to treat PMOP. Previous studies have demonstrated its efficacy, but the mechanism of action remains uncharacterized. PURPOSE: This study aims to observe and discuss the mechanism of Jiangu granule to ameliorate bone loss in OVX rats by regulating the gut microbiota (GM)-short-chain fatty acids (SCFAs)- Treg/Th17 axis. METHODS: Female SD rats were divided into the sham operation (S), Jiangu granule (J), and model group (M). Bilateral ovaries were surgically removed from the rats in the J and M groups. After 6 and 12 weeks, rats were sacrificed, and femur, tibia, vertebrae, serum, spleen, colon, and feces samples were collected. We detected the strength of bones, gut microbiota structure, and SCFAs in feces, the Treg and Th17 cell levels in the spleen, and cytokine levels in the serum. RESULT: Jiangu granule restored the abundance of gut microbiota, increased the content of SCFAs, reduced the permeability of colon epithelium, increased the proportion of Treg cells in the spleen, changed the osteoimmunomodulation-related cytokines, effectively prevented bone loss, and enhanced bone strength. CONCLUSION: Jiangu granule can effectively improve bone loss in OVX rats, possibly by regulating the "GM-SCFAs-Treg/Th17″ axis.

Hypeisoxazole A, a Racemic Pair of Tetrahydroisoxazole-Fused Benzylisoquinoline Alkaloids from Hypecoum erectum and Structural Revision of Hypecoleptopine.

(±)-Hypeisoxazole A (1), a racemic pair of rearranged benzylisoquinoline alkaloids possessing an unprecedented diindeno[2,1-c:2',1'-d] isoxazole scaffold, was isolated from the medicinal herb Hypecoum erectum, along with hypecoleptopine (2), whose structure is now revised as a novel spiro-benzylisoquinoline alkaloid with a 6/6/5/6/6 skeleton. Their structures were determined by comprehensive spectroscopic and spectrometric analyses, X-ray diffraction, and computational studies. Racemic mixture of 2 and its pure enantiomers modulated neuronal excitability activity.

Isolation and Characterization of Bioactive Proteoglycan-Lipid Nanoparticles from Freshwater Clam (Corbicula fluminea Muller) Soup.

Nanoparticles can be prepared by several sophisticated processes but until now, it cannot be prepared by simple home cooking. Here, we report that two incidental food nanoparticles (iFNPs) consisting of proteoglycans and phytosterols were isolated from soup made from freshwater clam (Corbicula fluminea Muller), a renowned folk remedy for liver problems in China and other parts of East Asia. These two bioactive iFNPs were obtained and characterized by anionic exchange chromatography coupled with multi-angle laser light scattering measurement. Their hydrodynamic diameters and ζ-potentials were 50 ± 0.2 nm and -28.0 mV and 67 ± 0.4 nm and -9.96 mV, respectively. FT-IR revealed that the proteoglycans in the particles contained α-type heteropolysaccharides. Both iFNPs were resistant to pH changes and separation by mechanical force but responsive to temperature changes. They effectively inhibited cholesterol uptake in vitro, which resonates with the traditional belief that freshwater clam soup provides hepatoprotective benefits. This study suggests that these two proteoglycan-lipid iFNPs are the active moieties and offers a supramolecular structure-based approach to study the function of such complex matrices derived from food.

Effect of Qing'e Decoction on Leptin/Leptin Receptor and Bone Metabolism in Naturally Aging Rats.

Senile osteoporosis (SOP) is a common disease that has decreased bone strength as its main symptom. There is currently no medication that can treat SOP, and traditional Chinese medicine has advantages in slowing down bone aging. The present study aimed to observe the effects of Qing'e decoction on leptin, leptin receptor, sex hormone, and biochemical markers of bone metabolism in naturally aging rats and to explore its mechanism in regulating bone metabolism. The results revealed that, with the increase in age, the bone mineral density (BMD), bone strength, bone trabecula sparse, serum levels of leptin receptor (LEP-R), estradiol (E2), testosterone (T), core binding-factor α-1 (Cbfα-1), collagen-I (COL-I) and osteocalcin (OC), and the mRNA levels of leptin (LEP) and LEP-R in bone tissue decreased, while serum LEP levels increased in the female and male NS groups. The serum levels of LEP, LEP-R, E2, T, osteoprotegerin, Cbfα-1, COL-I, OC and bone alkaline phosphatase, and the mRNA levels of LEP and LEP-R in bone tissue in the female and male QED groups were higher than those in the same age and sex NS group, while the BMD, bone trabecular area percentage, maximum load, and maximum stress in the female and male QED groups were significantly higher than those in the same age and sex NS group. In conclusion, with the increase in age, the bone quality of naturally aging rats decreased gradually. Qing'e decoction can regulate the bone metabolism and increase the bone quality and delay bone aging, which may be achieved by increasing sex hormone, LEP, and LEP-R levels.

[Effect of calcium on ion contents and expression of photosynthetic related genes in honeysuckle under salt stress].

Exogenous calcium can enhance the resistance of certain plants to abiotic stress. Research have demonstrated that exogenous calcium could enhances the resistance of honeysuckle under salt stress by promoting the transmission of photosynthetic electrons.The aim of this study was to investigate the effects of exogenous calcium on the contents of Na~+,K~+,Ca~(2+),Mg~(2+)and the expression of photosynthetic related genes Cab and rbc L. In this study,we used ICP-OES to analysis ion contents and used qRT-PCR to analysis the expression patterns of Cab and rbc L. The results showed that CaCl_2 significantly enhanced the K~+-Na~+,Ca~(2+)-Na~+,Mg~(2+)-Na+ratio of honeysuckle treated with 50 and 100 mmol·L~(-1) NaCl. Meanwhile,Cab and rbc L were significantly up-regulated under short-term salt stress,and CaCl_2 promoted this trend. From the two gene expression patterns,rbc L rapidly up-regulated on the first day of stress and then decreased,and was more sensitive to environmental changes. In summary,exogenous calcium could alleviate salt stress and increase plant development by increasing intracellular K~+-Na~+,Ca~(2+)-Na~+,Mg~(2+)-Na+ratio,and the transient overexpression of Cab and rbc L.

[Vinegar processing attenuates toxicity on IEC-6 cells caused by chloroform extraction of Daphne genkwa].

To screen the toxic polar fractions of Daphne genkwa, compare the toxicity of D. genkwa on crypts epithelial cells IEC-6 before and after vinegar processing, and preliminarily investigate the mechanism of D. genkwa vinegar processing on toxicity reducing. The proliferation of IEC-6 cells was observed by MTT. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), as well as the enzyme activity of Na⁺-K⁺-ATPase and Ca²âº-Mg²âº-ATPase were determined in IEC-6 cells to evaluate the oxidative damages degree of IEC-6 cells. The apoptosis and cell cycle were analyzed by Flow Cytometry. The results showed that the dichloromethane extraction was the toxic polar fraction of D. genkwa, and after vinegar processing, the toxicity of dichloromethane fraction was significantly reduced (P<0.01). As compared with the blank control group, the dichloromethane fraction of D. genkwa can obviously decrease the levels of SOD, Na⁺-K⁺-ATPase, Ca²âº-Mg²âº-ATPase (P<0.01) and content of GSH, but increase the level of LDH and MDA in cell supernatant (P<0.01). Besides, it obviously increased the early and late apoptotic rate of IEC-6 cells, obviously decreased the proportion of G1stage cells, increased the ratio of S stage cells and M stage cells (P<0.01). After vinegar processing, as compared with D. genkwa groups of various doses, it can significantly increase the levels of SOD, Na⁺-K⁺-ATPase, Ca²âº-Mg²âº-ATPase (P<0.01) and content of GSH, decrease the level of LDH, MDA(P<0.01), significantly decrease the early and late apoptosis rate of IEC-6 cells (P<0.01), increase the proportion of G1stage cells, and decrease the ratio of S stage cells and M stage cells (P<0.01). Vinegar processing can reduce the toxicity of dichloromethane fraction of D. genkwa, and its mechanism may be associated with improving the activity of antioxidant enzymes and permeability in IEC-6 cells, and decreasing the oxidative damage.

Study protocol for One Health data collections, analyses and intervention of the Sino-Swedish integrated multisectoral partnership for antibiotic resistance containment (IMPACT).

INTRODUCTION: To effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked. METHODS AND ANALYSIS: Both quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum ß-lactamase and carbapenemase-producing Enterobacteriaceae from pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistant Staphylococcus aureus in humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention. ETHICS: Ethics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.

Antihypertensive properties of tilapia (Oreochromis spp.) frame and skin enzymatic protein hydrolysates.

Proteins from tilapia frame and skin can potentially be precursors of antihypertensive peptides according to the result of BIOPEP analyses. The aim was to generate peptides with inhibitory effects against angiotensin-converting enzyme (ACE) and renin from tilapia frame and skin protein isolates (FPI and SPI). The most active hydrolysate was then tested for blood pressure-lowering ability in spontaneously hypertensive rats (SHRs). Tilapia frame and skin protein hydrolysates (FPHs and SPHs) were respectively produced from FPI and SPI hydrolysis using pepsin, papain, or bromelain. The ACE-inhibitory activities of tilapia protein hydrolysates with varying degree of hydrolysis (DH) were evaluated. In order to enhance the activity, the hydrolysate was fractionated into four fractions (<1 kDa, 1-3 kDa, 3-5 kDa, and 5-10 kDa) and the one with the greatest ability to inhibit in vitro ACE and renin activities was subjected to oral administration (100 mg/kg body weight) to SHRs. Systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), and heart rates (HR) were subsequently measured within 24 h. The pepsin-hydrolyzed FPH (FPHPe) with the highest DH (23%) possessed the strongest ACE-inhibitory activity (IC50: 0.57 mg/mL). Its <1 kDa ultrafiltration fraction (FPHPe1) suppressed both ACE (IC50: 0.41 mg/mL) and renin activities more effectively than larger peptides. In addition, FPHPe1 significantly (p < 0.05) reduced SBP (maximum -33 mmHg), DBP (maximum -24 mmHg), MAP (maximum -28 mmHg), and HR (maximum -58 beats) in SHRs. FPHPe1 showed both in vitro and in vivo antihypertensive effects, which suggest tilapia processing coproducts may be valuable protein raw materials for producing antihypertensive peptides.

Structural characterization and immunostimulatory activity of a novel linear α-(1→6)-D-glucan isolated from Panax ginseng C. A. Meyer.

Panax ginseng C. A. Meyer is a well-known plant medicine in the world. Ginseng polysaccharides mainly contain starch-like glucan and pectin. In this paper, a novel glucan WGPA-UH-N1 was purified from ginseng pectin by the treatment of de-esterification and endo-polygalacturonase, followed by the chromatographies on DEAE-Sepharose Fast Flow and Sephadex G-50 column. WGPA-UH-N1 has molecular weight about 17 kDa. WGPA-UH-N1 was determined to be a linear α-(1→6)-D-glucan without side chains by FT-IR, (13)C-NMR, (1)H-NMR, HMQC and HMBC spectra. It is the first time to isolate a linear α-(1→6)-D-glucan from Panax ginseng C. A. Meyer. Immunological activity assays showed that WGPA-UH-N1, although not effective on the phagocytosis of macrophage, could significantly induce lymphocyte proliferation without mitogenic stimuli at 1.0 mg/mL or with LPS at 0.5 mg/mL, also significantly increase NO production at the range of 0.1-1.0 mg/mL in a dose-dependent manner. The immunological activities of WGPA-UH-N1 are different from those of the ß-(1→6)-D-glucan (BIWP2) isolated from the fruit bodies of Bulgaria Inquinans (Fries).

[Survey clinical evidence of acupuncture therapy for depressive neurosis].

OBJECTIVE: To evaluate the clinical studies of acupuncture for treatment of depressive neurosis, collect the high quality evidence relative to clinical acupuncture practice for clinical decision-making reference. METHODS: Around crucial common questions of acupuncture clinical practice, the documents of clinical study were comprehensively retrieved. According to 5-grade criterion of evidence-based medicine, the evidence from high to low level were selected to answer corresponding clincal questions and RevMan 5.0.20 was used to analyze the final indicator. RESULTS: Nineteen documents of clinical study accord with the inclusive criterion were retrieved. Level-A evidence showed effectiveness of acupuncture. Acupuncture might be superior or equal to fluoxetine, with little adverse effect and high safety. Level-C evidence showed acupuncture might be superior or equal to Amitriptyline, with little adverse effect and high safety. And no relative clinicial evidence compared effect of acupuncture with that of psychotherapy or behavior therapy. Only one level-C evidence showed there was no effect difference between acupuncture combined with bloodletting therapy and bloodletting alone. Two level-C evidence showed the effect of acupuncture combined with western medicine was superior to that of medicine alone, eg. catgut embedding therapy combined with Fluoxetine, electroacupuncture combined with Seroxat. CONCLUSION: Acupuncture for depressive nerosis has a positive effect. Acupuncture has an equal effect compared with western medicine, while strictly designed equivalent and non-inferior studies are demanded. The effect of acupuncture combined with medicine has some advantage, but need high quality studies to verify.

[Graded-disease-spectrum of the nervous system of acu-moxibustion therapy was determined based on its clinical efficacy and by fuzzy comprehensive estimation technique].

OBJECTIVE: To determine the graded-disease-spectrum of the nervous system of acu-moxibustion treatment based on its clinical efficacy. METHODS: We carried out a cross-sectional academic sample investigation on the graded-disease-spectrum of acu-moxibustion by collecting and analyzing data from the self-administered questionnaires which were completed by professional persons who have high-ranking professional titles (associate chief physicians and chief physicians) and are majoring in acupuncture and moxibustion. Then, the collected experts' opinions were analyzed by fuzzy comprehensive estimation technique and statistical processing. RESULTS: A total of 58 medical conditions involving 4 grades and 126 subtypes were included and analyzed. The Grade I contains 14 subtypes as Bell's palsy (in the acute stage and convalescence stage), primary sciatic neuralgia, migraine (mild type and moderate type), etc. which can be relieved by using acu-moxibustion therapy only. The Grade II contains 53 subtypes, such as transient cerebral ischemic attack, acute cerebrovascular disease (in the convalescence stage and sequelae stage), chronic Bell's palsy (sequelae), Hunt's facial palsy, etc. which can be relieved by using acu-moxibustion as the main therapy. The Grade III contains 22 subtypes, such as acute stage of ischemic cerebrovascular disease (with coma and without coma), acute stage of hemorrhagic ischemic cerebrovascular disease (with coma and without coma), etc. which may be relieved to a certain degree by using acu-moxibustion as the supplementary or main therapy. The Grade IV contains 37 subtypes, such as Wohlfart-Kugelberg-Welander disease, myasthenia gravis (type III and type IV), myasthenia gravis of medicinal herbs resource, chorea major, etc. whose clinical effects are not known if treated with acu-moxibustion. CONCLUSION: Acu-moxibustion therapy has apparent advantages in the treatment of different clinical conditions of the nervous system.

[Systematic evaluation of therapeutic effect of acupuncture for treatment of simple obesity].

OBJECTIVE: To evaluate the therapeutic effect of acupuncture for treatment of simple obesity, and to analyze the current situation of clinical studies. METHODS: Randomized controlled trials (RCTs) involving acupuncture treatment for simple obesity were searched from PubMed (1979-2008), OVID (1979-2008), EBSCO (1973-2008), Cochrane Library (Issue 2, 2008), CBM (1978-2008), CNKI (1979-2008), VIP (1989-2008) and WanFang Database (1998-2008). Literatures were enrolled focusing on RCTs related to acupuncture treatment for simple obesity; the quality of literatures were evaluated by two evaluators unaidedly. Meta-analyses were conducted with the Cochrane Collaboration's RevMan 4.2.8 software. RESULTS: Eight papers including 1,017 cases, conformed with the enrolled criteria. Meta-analyses showed that there were significant difference between acupuncture groups and western medicine groups in the effective rate [combined RR (fixed effects model) = 1.11, 95% CI (1.05, 1.18), P=0.0006]. There was a significant difference between acupuncture and Sibutramine in the body mass [combined WMD (fixed effects model) = 1.94, 95%CI (1.73, 2.16), P<0.00001] and body mass index (BMI) [combined WMD (fixed effects model) = 0.52, 95% CI (0.33, 0.70), P<0.00001]. However, acupuncture was not superior to Sibutramine in hip circumference (HC) [combined WMD (fixed effects model) = -0.35, 95% CI (-0.56, -0.15), P<0.0007]. CONCLUSION: For treating simple obesity, besides reasonable diet and exercise, acupuncture is safe and effective, which may be more effective than routine western medicine. The quantity of literature was limited and the quality of some literatures was low. Thus, more high-quality and large-scale of RCTs are needed.

Anti-oxidative and anti-inflammatory activities of two different species of a Chinese herb I-Tiao-Gung.

The anti-oxidative and anti-inflammatory activities of two different species of traditional Chinese medicines that shared the same name have been studied. The extracts of Glycine radix have higher activities in free radical-scavenging activity determined with DPPH, reduction in hemoglobin-catalyzed lipid auto-oxidation and inhibition of the lipoxygenase (LOX) and cyclooxygenase (COX)-catalyzed arachidonate oxidation compared to the activities of extract of Flemingia. One of the significant bioactive constituents of Glycine radix has been isolated and identified as daidzein.