Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Salidroside protects pulmonary artery endothelial cells against hypoxia-induced apoptosis via the AhR/NF-κB and Nrf2/HO-1 pathways.

BACKGROUND: The apoptosis of pulmonary artery endothelial cells (PAECs) is an important factor contributing to the development of pulmonary hypertension (PH), a serious cardio-pulmonary vascular disorder. Salidroside (SAL) is a bioactive compound derived from an herb Rhodiola, but the potential protective effects of SAL on PAECs and the underlying mechanisms remain elusive. PURPOSE: The objective of this study was to determine the role of SAL in the hypoxia-induced apoptosis of PAECs and to dissect the underlying mechanisms. STUDY DESIGN: Male Sprague-Dawley (SD) rats were subjected to hypoxia (10% O2) for 4 weeks to establish a model of PH. Rats were intraperitoneally injected daily with SAL (2, 8, and 32 mg/kg/d) or vehicle. To define the molecular mechanisms of SAL in PAECs, an in vitro model of hypoxic cell injury was also generated by exposed PAECs to 1% O2 for 48 h. METHODS: Various techniques including hematoxylin and eosin (HE) staining, immunofluorescence, flow cytometry, CCK-8, Western blot, qPCR, molecular docking, and surface plasmon resonance (SPR) were used to determine the role of SAL in rats and in PAECs in vitro. RESULTS: Hypoxia stimulation increases AhR nuclear translocation and activates the NF-κB signaling pathway, as evidenced by upregulated expression of CYP1A1, CYP1B1, IL-1ß, and IL-6, resulting in oxidative stress and inflammatory response and ultimately apoptosis of PAECs. SAL inhibited the activation of AhR and NF-κB, while promoted the nuclear translocation of Nrf2 and increased the expression of its downstream antioxidant proteins HO-1 and NQO1 in PAECs, ameliorating the hypoxia-induced oxidative stress in PAECs. Furthermore, SAL lowered right ventricular systolic pressure, and decreased pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-exposed rats. CONCLUSIONS: SAL may attenuate the apoptosis of PAECs by suppressing NF-κB and activating Nrf2/HO-1 pathways, thereby delaying the progressive pathology of PH.

Effects of Apple Polyphenols and Taurine on Growth Performance, Tissue Morphology, and Lipid and Glucose Metabolism in Rice Field Eel (Monopterus albus) Fed High Oxidized Fish Oil.

The aim of this trial was to investigate the effects of apple polyphenols (AP) and taurine (TA) on the growth performance, tissue morphology, and lipid and glucose metabolism in rice field eel fed diets with high oxidized fish oil (OFO). A 10-week feeding experiment was conducted using juveniles (initial body weight 16.66 ± 0.02 g) fed five different diets. Three diets were formulated with various levels of OFO at 9.5, 600, and 800 meq·kg-1 and named as Control, POV600, and POV800 diet, respectively. The other two diets were POV600 and POV800 supplemented with 0.5% AP and 0.2% TA, respectively. Compared to the Control group, only the eels fed POV800 exhibited an increase in weight gain and specific growth rate along with a reduction in feed conversion ratio. AP and TA did not affect growth performance; juveniles fed AP, however, showed a decrease in liver weight. Both POV600 and POV800 decreased nuclei number and increased vacuoles size in the liver. POV800 damaged the intestinal structure integrity and reduced goblet cells number. AP repaired the liver damage on nuclei number and vacuoles size in fish fed with POV600 diet, while TA mitigated intestinal histopathological damage on intact structure and goblet cells number. The mRNA expression level of liver ampkα in fish fed AP was upregulated, while dietary TA upregulated the mRNA expression levels of liver ampkα and accα. In the muscle, POV600 downregulated mRNA expression levels of accα, cpt1, and lipin, whereas POV800 upregulated mRNA expression levels of accα, pparα, and lipin. Dietary AP and TA could counteract the effects of POV600 and POV800 diet on muscle lipid metabolism. Both POV600 and POV800 diets upregulated mRNA expression levels of liver pck1 and gsk3α. AP and TA both downregulated mRNA expression level of liver pck1, while only TA downregulated the expression of liver gsk3α. AP increased the mRNA expression level of gsk3α in muscle. In summary, inclusion of AP and TA did not affect growth performance but showed a potential to alleviate liver or intestinal damages induced by a high OFO diet. Dietary AP and TA were also found to regulate mRNA expression of genes related to lipid and glucose metabolism.

Cinnamaldehyde induces apoptosis and enhances anti-colorectal cancer activity via covalent binding to HSPD1.

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection and adjuvant radiotherapy/chemotherapy are the mainstays of CRC treatment, the efficacy is unsatisfactory due to several limitations, including high drug resistance. Accordingly, there is a dire need for new drugs or a novel combination approach to treat this patient population. Herein, we found that cinnamaldehyde (CA) could exert an antitumor effect in HCT-116 cell lines. Target fishing, molecular imaging, and live-cell tracing using an alkynyl-CA probe revealed that the heat shock 60 kDa protein 1 (HSPD1) protein was the target of CA. The covalent binding of CA with HSPD1 altered its stability. Furthermore, our results demonstrated that CA could induce cell apoptosis by inhibiting the PI3K/Akt signaling pathway and enhanced anti-CRC activity both in vitro and in vivo. Meanwhile, CA combined with different chemotherapeutic agents was beneficial to patients resistant to anti-CRC drug therapy.

Oral Liushen pill for patients with COVID-19: A prospective randomized controlled trial.

We examined the efficacy and safety of Liushen pill combined with basic treatment for patients with COVID-19. In total, 181 patients hospitalized with COVID-19, classified as asymptomatic mild type, were randomly divided into the experimental (n = 91) and control (n = 90) groups and were administered placebo (Maizao decoction) and Maizao decoction and Liushen pill, in addition to standard care, respectively. The negative conversion rate of nucleic acid (Day 7), hospital discharge rate (Days 8, 10, and 14), symptom disappearance rate (Days 3, 5, and 7), inflammatory cytokine levels, and adverse events were compared between the groups. The negative viral conversion rate was significantly higher in the experimental than in the control group (48.35 vs. 31.11%, p < 0.05). Subgroup analysis showed a similar significant trend when the Ct value was ≤30 at baseline. After 10 days, the hospital discharge rate was significantly higher in the experimental than in the control group (69.23 vs. 53.33%, p < 0.05). After 3-day medication, the headache symptoms significantly disappeared in the experimental (88.57%) compared to the control group (63.33%) (p < 0.05). After 5 days, the symptom disappearance rates of headache and cough were significantly higher in the experimental (97.14%) than in the control group (97.14 vs. 80.00, p < 0.05; 82.65 vs. 58.93%, p < 0.01, respectively). Posttreatment, the procalcitonin level was significantly lower in the experimental than in the control group (0.09 ± 0.00 vs. 0.14 ± 0.05 ng/L; p < 0.05). There were no significant between-group differences in clinical safety test indices. Early intervention with Liushen pill improved cough and headache and increased negative viral conversion and discharge rate.

Vitiligo: An immune disease and its emerging mesenchymal stem cell therapy paradigm.

Melanocyte damage, innate immune response, adaptive immune response, and immune inflammatory microenvironment disorders are involved in the development of the immunological pathogenic mechanism of vitiligo. Mesenchymal stem cells are considered an ideal type of cells for the treatment of vitiligo owing to their low immunogenicity, lower rates of transplant rejection, and ability to secrete numerous growth factors, exosomes, and cytokines in vivo. The regulation of signaling pathways related to oxidative stress and immune imbalance in the immunological pathogenesis of vitiligo can improve the immune microenvironment of tissue injury sites. In addition, co-transplantation with melanocytes can reverse the progression of vitiligo. Therefore, continuous in-depth research on the immunopathogenic mechanism involved in this disease and mesenchymal stem cell-based therapy is warranted for the treatment of vitiligo in the future.

Antioxidant mechanisms of mesenchymal stem cells and their therapeutic potential in vitiligo.

Vitiligo is a skin pigmentation disorder caused by melanocyte damage or abnormal function. Reac-tive oxygen species Reactive oxygen species can cause oxidative stress damage to melanocytes, which in turn induces vitiligo. Traditional treatments such as phototherapy, drugs, and other methods of treatment are long and result in frequent recurrences. Currently, mesenchymal stem cells (MSCs) are widely used in the research of various disease treatments due to their excellent paracrine effects, making them a promising immunoregulatory and tissue repair strategy. Furthermore, an increasing body of evi-dence suggests that utilizing the paracrine functions of MSCs can downregulate oxidative stress in the testes, liver, kidneys, and other affected organs in animal models of certain diseases. Addition-ally, MSCs can help create a microenvironment that promotes tissue repair and regeneration in are-as with oxidative stress damage, improving the disordered state of the injured site. In this article, we review the pathogenesis of oxidative stress in vitiligo and promising strategies for its treatment.

Integrative Metabolomics and Proteomics Detected Hepatotoxicity in Mice Associated with Alkaloids from Eupatorium fortunei Turcz.

The traditional Chinese herbal medicine Eupatorium fortunei Turcz. (E. fortunei) has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, E. fortunei contains multiple pyrrolizidine alkaloids (PAs). This study aimed to investigate the hepatotoxicity of total alkaloids in E. fortunei (EFTAs) and identify the toxic mechanisms of EFTAs on hepatocytes. Liquid chromatography with a tandem mass spectrometry assay with reference standards indicated that EFTAs mainly consisted of eight PAs whose content accounted for 92.38% of EFTAs. EFTAs markedly decreased mouse body and liver weights and increased the contents of AST and ALT. The histopathological assays demonstrated that, after exposition to EFTAs, the structures of hepatocytes were damaged and the fibrosis and apoptosis in hepatocytes were accelerated. Moreover, EFTAs increased the serum level of inflammatory cytokines and aggravated circulating oxidative stress. A combination of hepatic proteomics and metabolomics was used to investigate the toxic mechanisms of EFTAs. The study revealed that EFTAs seriously disrupted glycerophospholipid metabolism by upregulating the contents of lysophosphatidylglycerol acyltransferase 1 and phosphatidylinositol and downregulating the contents of choline/ethanolamine kinase beta, choline-ethanolamine phosphotransferase 1, phospholipase D4, 1-acylglycerophosphocholine, phosphatidylcholine, and dihydroxyacetone phosphate in the liver, resulting in detrimental inflammation, fibrosis, and apoptosis. This study revealed that EFTAs induced severe hepatotoxicity by disrupting glycerophospholipid metabolism.

Nitrogen-inducible GLK1 modulates phosphate starvation response via the PHR1-dependent pathway.

Phosphorus (P) is a limiting nutrient for plant growth and productivity. Thus, a deep understanding of the molecular mechanisms of plants' response to phosphate starvation is significant when breeding crops with higher phosphorus-use efficiency. Here, we found that GARP-type transcription factor GLK1 acted as a positive regulator for phosphate-starvation response (PSR) via the PHR1-dependent pathway in Arabidopsis thaliana. GLK1 increased the transcription activity of PHR1 through the direct physical interaction and regulated the multiple responses to inorganic orthophosphate (Pi) starvation. Nitrogen (N) is a key factor in the regulation of PSR. We also found that the N status controlled the function of the GLK1-PHR1 signaling module under Pi-deficient (LP) conditions by regulating the accumulation of GLK1 and PHR1. Ultimately, we showed that the presence of GLK1 effectively promoted the protein accumulation of PHR1 at low N concentrations, and this action was helpful to maintain the activation of PSR. According to these findings, we establish the working model for GLK1 in PSR and propose that GLK1 mediates the interaction between N and P by influencing the effect of N on PHR1 in Arabidopsis thaliana.

Electroacupuncture Ameliorates Intestinal Barrier Destruction in Mice With Bile Duct Ligation-Induced Liver Injury by Activating the Cholinergic Anti-Inflammatory Pathway.

OBJECTIVES: Electroacupuncture (EA) at Zusanli (ST36) can attenuate inflammation in different rodent models. However, the therapeutic mechanisms underlying its action in inhibiting intestinal barrier destruction and liver injury in cholestasis mice have not been clarified. This study aimed at investigating whether EA at ST36 could activate the cholinergic anti-inflammatory pathway to inhibit intestinal barrier destruction and liver injury in cholestasis mice. MATERIALS AND METHODS: Male Hmox1floxp/floxp C57BL/6 mice were randomized and subjected to a sham or bile duct ligation (BDL) surgery. The BDL mice were randomized and treated with, or without (BDL group), sham EA at ST36 (BDL+sham-ST36) or EA at ST36 (BDL+ST36), or received α-bungarotoxin (α-BGT), a specific inhibitor of nicotinic acetylcholine receptor α7 subunit (α7nAChR), before stimulation (BDL+ST36+α-BGT). These mice, together with a group of intestine-specific heme oxygenase-1 (HO-1) knockout (KO) Villin-Cre-HO-1-/- mice, were monitored for their body weights before and 14 days after BDL. The levels of plasma cytokines and liver injury-related alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by enzyme-linked immunoassay, and pathological changes in the intestinal mucosa and liver fibrosis as well as intestinal barrier permeability in individual mice were examined by histology and immunohistochemistry. The levels of α7nAChR, HO-1, ZO-1, Occludin, Claudin-1, and NF-κBp65 expression and NF-κBp65 phosphorylation in intestinal tissues were quantified. RESULTS: Compared with the sham group, BDL significantly increased the levels of plasma interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor α, ALT, and AST and caused intestinal mucosal damages, high permeability, and liver fibrosis in mice, which were remarkably mitigated, except for further increased levels of plasma IL-10 in the BDL+ST36 group of mice. Similarly, EA at ST36 significantly up-regulated α7nAChR and HO-1 expression; mitigated the BDL-decreased ZO-1, Occludin, and Claudin-1 expression; and attenuated the BDL-increased NF-κBp65 phosphorylation in intestinal tissues of mice. The therapeutic effects of EA at ST36 were significantly abrogated by pretreatment with α-BGT or HO-1 KO. CONCLUSION: EA at ST36 inhibits the BDL-induced intestinal mucosal damage and liver fibrosis by activating the HO-1 cholinergic anti-inflammatory pathway in intestinal tissues of mice.

Hydrogen-oxygen therapy alleviates clinical symptoms in twelve patients hospitalized with COVID-19: A retrospective study of medical records.

ABSTRACT: A global public health crisis caused by the 2019 novel coronavirus disease (COVID-19) leads to considerable morbidity and mortality, which bring great challenge to respiratory medicine. Hydrogen-oxygen therapy contributes to treat severe respiratory diseases and improve lung functions, yet there is no information to support the clinical use of this therapy in the COVID-19 pneumonia.A retrospective study of medical records was carried out in Shishou Hospital of Traditional Chinese Medicine in Hubei, China. COVID-19 patients (aged ≥ 30 years) admitted to the hospital from January 29 to March 20, 2020 were subjected to control group (n = 12) who received routine therapy and case group (n = 12) who received additional hydrogen-oxygen therapy. The clinical characteristics of COVID-19 patients were analyzed. The physiological and biochemical indexes, including immune inflammation indicators, electrolytes, myocardial enzyme profile, and functions of liver and kidney, were examined and investigated before and after hydrogen-oxygen therapy.The results showed significant decreases in the neutrophil percentage and the concentration and abnormal proportion of C-reactive protein in COVID-19 patients received additional hydrogen-oxygen therapy.This novel therapeutic may alleviate clinical symptoms of COVID-19 patients by suppressing inflammation responses.

Traditional Chinese medicine as a therapeutic option for cardiac fibrosis: Pharmacology and mechanisms.

Cardiovascular diseases are one of the leading causes of death worldwide and cardiac fibrosis is a common pathological process for cardiac remodeling in cardiovascular diseases. Cardiac fibrosis not only accelerates the deterioration progress of diseases but also becomes a pivotal contributor for futile treatment in clinical cardiovascular trials. Although cardiac fibrosis is common and prevalent, effective medicines to provide sufficient clinical intervention for cardiac fibrosis are still unavailable. Traditional Chinese medicine (TCM) is the natural essence experienced boiling, fry, and other processing methods, including active ingredients, extracts, and herbal formulas, which have been applied to treat human diseases for a long history. Recently, research has increasingly focused on the great potential of TCM for the prevention and treatment of cardiac fibrosis. Here, we aim to clarify the identified pro-fibrotic mechanisms and intensively summarize the application of TCM in improving cardiac fibrosis by working on these mechanisms. Through comprehensively analyzing, TCM mainly regulates the following pathways during ameliorating cardiac fibrosis: attenuation of inflammation and oxidative stress, inhibition of cardiac fibroblasts activation, reduction of extracellular matrix accumulation, modulation of the renin-angiotensin-aldosterone system, modulation of autophagy, regulation of metabolic-dependent mechanisms, and targeting microRNAs. We also discussed the deficiencies and the development direction of anti-fibrotic therapies on cardiac fibrosis. The data reviewed here demonstrates that TCM shows a robust effect on alleviating cardiac fibrosis, which provides us a rich source of new drugs or drug candidates. Besides, we also hope this review may give some enlightenment for treating cardiac fibrosis in clinical practice.

Comparison and Analysis on the Existing Single-Herbal Strategies against Viral Myocarditis.

Purpose: Herbal medicine is one of crucial symbols of Chinese national medicine. Investigation on molecular responses of different herbal strategies against viral myocarditis is immeasurably conducive to targeting drug development in the current international absence of miracle treatment. Methods: Literature retrieval platforms were applied in the collection of existing empirical evidences for viral myocarditis-related single-herbal strategies. SwissTargetPrediction, Metascape, and Discovery Studio coordinating with multidatabases investigated underlying target genes, interactive proteins, and docking molecules in turn. Results: Six single-herbal medicines consisting of Huangqi (Hedysarum Multijugum Maxim), Yuganzi (Phyllanthi Fructus), Kushen (Sophorae Flavescentis Radix), Jianghuang (Curcumaelongae Rhizoma), Chaihu (Radix Bupleuri), and Jixueteng (Spatholobus Suberectus Dunn) meet the requirement. There were 11 overlapped and 73 unique natural components detected in these herbs. SLC6A2, SLC6A4, NOS2, PPARA, PPARG, ACHE, CYP2C19, CYP51A1, and CHRM2 were equally targeted by six herbs and identified as viral myocarditis-associated symbols. MCODE algorithm exposed the hub role of SRC and EGFR in strategies without Jianghuang. Subsequently, we learned intermolecular interactions of herbal components and their targeting heart-tissue-specific CHRM2, FABP3, TNNC1, TNNI3, TNNT2, and SCN5A and cardiac-myocytes-specific IL6, MMP1, and PLAT coupled with viral myocarditis. Ten interactive characteristics such as π-alkyl and van der Waals were modeled in which ARG111, LYS253, ILE114, and VAL11 on cardiac troponin (TNNC1-TNNI3-TNNT2) and ARG208, ASN106, and ALA258 on MMP1 fulfilled potential communicating anchor with ellagic acid, 5α, 9α-dihydroxymatrine, and leachianone g via hydrogen bond and hydrophobic interaction, respectively. Conclusions: The comprehensive outcomes uncover differences and linkages between six herbs against viral myocarditis through component and target analysis, fostering development of drugs.

Compound Danshen Dripping Pill ameliorates post ischemic myocardial inflammation through synergistically regulating MAPK, PI3K/AKT and PPAR signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Danshen Dripping Pill (CDDP), composed of Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H. Chen and Borneol, is a famous traditional Chinese medicine formula which has made great achievements in the treatment of ischemic heart disease, but the profound mechanism of CDDP improving post ischemic myocardial inflammation hasn't been clearly discussed. AIM OF THE STUDY: The aim of this study was to explore the biological mechanism of constituents in CDDP synergistically improving post ischemic myocardial inflammation. MATERIALS AND METHODS: The pharmacologic studies were applied to assess the cardio protection effect of CDDP in acute myocardial ischemic rats. To identify the anti-inflammatory ingredients in CDDP, an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with a dual-luciferase reporter assay for NF-κB inhibition were used. The network pharmacology and molecular docking assay were adopted to predict targets of anti-inflammatory ingredients and then the regulation effects of these active components on their targets were also verified. RESULTS: Our results indicated that CDDP exerted an excellent cardio protection effect by reversing echocardiographic abnormalities, attenuating histopathological lesion, ameliorating circulating myocardial markers and inflammation cytokines. Tanshinol, salvianolic acid B (Sal B), tanshinone IIA (Tan IIA) and notoginsenoside R1 (NGR1) were the pivotal anti-inflammatory ingredients in CDDP. The anti-inflammatory mechanism is that tanshinol and Sal B respectively targeted on PPARγ and JNK, while Tan IIA worked on AKT1 and NGR1 bound to PI3K. CONCLUSIONS: Our results firstly demonstrated that CDDP effectively ameliorated post ischemic myocardial inflammation through simultaneously modulating MAPK, PI3K/AKT and PPAR pathways in a multi-components synergetic manner.

Comparative Analysis on Single- and Multiherb Strategies in Coronary Artery Atherosclerosis Therapy.

Herbal medicine unswervingly serves human health by modernizing preparation and administration. Coronary artery atherosclerosis is a serious threat to human health and survival all over the world. Following experimental and clinical evidence, we collected four herbal treatments containing herbal strategy I (San Qi), II (Injectio Salvia Miltiorrhizae), III (Danhong injection), and IV (Taoren Honghua Jian granule) against coronary artery disease. In order to analyze their similarities and differences in controlling coronary artery atherosclerosis, we investigated each herb of four strategies and revealed that the number of active components and molecule targets is increasing with the herb category of herbal strategy. Nitric oxide-associated carbonate dehydratase activity and nitrogen metabolism are tacitly enriched by target corresponding genes with statistical significance in four strategies. The herbal strategy with multiherb not merely possesses more amounts and interactions of target proteins than the strategy with single-herb but also enlarges interaction partners of target proteins like PTPN11 and STAT3 in strategy II, III, and IV. Whereas single-herb also involves regulating network core proteins in consistent with compatibility, such as SRC and PIK3R1 that are mostly targeted by strategy I, III, and IV. Comparing the targets of the herbal strategies and three existing drugs (atenolol, pravastatin and propranolol) and the symbols of coronary artery atherosclerosis, we discovered that MAOA, HTR1A, and ABCG2 are overlapping in the three groups. Hence, our work enables people to better understand the connections and distinctions of single- and multiherb on the healing of coronary artery atherosclerosis.

Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice.

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

Polydopamine-carbon dots functionalized hollow carbon nanoplatform for fluorescence-imaging and photothermal-enhanced thermochemotherapy.

The low power photothermal therapy can reduce the tissue damage caused by laser irradiation, thus the near-infrared (NIR) absorbing vehicles with high photothermal conversion efficiency are demanded in the low power treatment. Herein, the NIR-absorbing agent polydopamine (PDA) and carbon dots (CDs) were gated on the openings of hollow mesoporous carbon (HMC) to construct a photothermal enhanced multi-functional system (HMC-SS-PDA@CDs). Interestingly, the fluorescence emission wavelength of HMC-SS-PDA@CDs was red-shifted by FRET effect between PDA and CDs, which solved the dilemma of fluorescence quenching of carbon-based materials and was more conducive to cell imaging. The modification of PDA@CDs not only acts as the gatekeepers to realize multi-responsive release of pH, GSH and NIR, but also endows the HMC vehicle with excellent photothermal generation capacity, the possibility for bio-imaging as well as the enhanced stability. Naturally, both the cytological level and the multicellular tumor sphere level demonstrate that the delivery system has good low-power synergistic therapeutic with combination index (CI) of 0.348 and imaging effects. Meanwhile, the combined treatment group showed the highest tumor inhibition rate of 92.6% at 0.75 W/cm2. Therefore, DOX/HMC-SS-PDA@CDs nano-platform had broad application prospects in low power therapy and convenient imaging of carbon-based materials.

Metagenomic analysis of the gut microbiome composition associated with vitamin D supplementation in Taiwanese infants.

Early childhood is a critical stage for the foundation and development of the gut microbiome, large amounts of essential nutrients are required such as vitamin D. Vitamin D plays an important role in regulating calcium homeostasis, and deficiency can impair bone mineralization. In addition, most people know that breastfeeding is advocated to be the best thing for a newborn; however, exclusively breastfeeding infants are not easily able to absorb an adequate amount of vitamin D from breast milk. Understanding the effects of vitamin D supplementation on gut microbiome can improve the knowledge of infant health and development. A total of 62 fecal sample from healthy infants were collected in Taiwan. Of the 62 infants, 31 were exclusively breastfed infants and 31 were mixed- or formula-fed infants. For each feeding type, one subgroup of infants received 400 IU of vitamin D per day, and the remaining infants received a placebo. In total, there are 15 breastfed and 20 formula-fed infants with additional vitamin D supplementation, and 16 breastfed and 11 formula-fed infants belong to control group, respectively. We performed a comparative metagenomic analysis to investigate the distribution and diversity of infant gut microbiota among different types of feeding regimes with and without vitamin D supplementation. Our results reveal that the characteristics of infant gut microbiota not only depend on the feeding types but also on nutrients intake, and demonstrated that the vitamin D plays an important role in modulating the infant gut microbiota, especially increase the proportion of probiotics in breast-fed infants.

Use of Herbal Medications for Treatment of Osteoarthritis and Rheumatoid Arthritis.

Arthritis is a chronic condition that affects nearly a quarter of the United States population. Osteoarthritis (OA) and rheumatoid arthritis (RA) are two major forms of arthritis associated with severe joint pain and reduced quality of life. Various pharmacological interventions may be utilized for arthritis treatment when non-pharmacological therapy is insufficient. However, pharmacological therapy can be associated with serious side effects and high costs. Therefore, alternative therapies have been under investigation. Herbal medications have shown the potential for safe and effective management of arthritis. For this review, we attempt to summarize the mechanisms, safety, and efficacy of herbal treatments for OA and RA. After searching electronic databases, we identified nine herbs among 23 clinical trials used for the treatment of OA or RA patients. Improvement of OA and RA symptoms, pain, and inflammation was demonstrated. The herbs exhibited strong anti-inflammatory and anti-oxidant activities, contributing to a reduction in inflammation and tissue damage. Several herbs elucidated new mechanisms for OA and RA treatment as well. Though these herbs have shown promise for OA and RA treatment, more studies and clinical trials are required for determining safety and efficacy, bioactivity, and optimal bioavailability.