Ziyuglycoside II attenuated OVX mice bone loss via inflammatory responses and regulation of gut microbiota and SCFAs.

BACKGROUND AND PURPOSE: Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. METHODS: We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. RESULTS: Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. CONCLUSIONS: Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.

Dietary supplementation of laminarin improves the reproductive performance of sows and the growth of suckling piglets.

BACKGROUND: Maternal nutrition is essential in keeping a highly efficient production system in the pig industry. Laminarin has been shown to improve antioxidant capacity, reduce the inflammatory response, and favor the homeostasis of intestinal microbiota. However, the effect of dietary supplementation of laminarin on the reproductive performance of sows and the growth of suckling offspring remains unknown. METHODS: A total of 40 Landrace × Yorkshire multiparous sows on d 85 of gestation, similar in age, body weight (BW), parity and reproductive performance, were randomly divided into four dietary treatments with 10 sows per treatment, receiving a control diet (basal pregnancy or lactating diets) and a basal diet supplemented with 0.025%, 0.05% and 0.10% laminarin, respectively. The experiment lasted from d 85 of gestation to d 21 of lactation. RESULTS: Laminarin supplementation linearly increased number born alive per litter (P = 0.03), average daily feed intake (ADFI, P < 0.01), and total milk yield of sows during the lactation of 1-21 d (P = 0.02). Furthermore, maternal laminarin supplementation increased the average daily gain (ADG) of piglets while tending to reduce the culling and death rate before weaning. In addition, alterations to the composition of colostrum and milk, as well as to serum inflammatory cytokines and immunoglobulins of sows were observed. The fecal microbiota profile of sows supported the improvement of reproductive performance in sows and the growth performance in suckling offspring. CONCLUSIONS: Dietary supplementation of laminarin during late pregnancy and lactation could significantly improve reproductive performance of sows and growth performance of piglets.

Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis.

The normal function of skeletal muscle and adipose tissue ensures whole-body glucose homeostasis. Ca2+ release channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) plays a vital role in regulating diet-induced obesity and disorders, but its functions in peripheral tissue regulating glucose homeostasis remain unexplored. In this study, mice with Ip3r1 specific knockout in skeletal muscle or adipocytes were used for investigating the mediatory role of IP3R1 on whole-body glucose homeostasis under normal or high-fat diet. We reported that IP3R1 expression levels were increased in the white adipose tissue and skeletal muscle of diet-induced obese mice. Ip3r1 knockout in skeletal muscle improved glucose tolerance and insulin sensitivity of mice on a normal chow diet, but worsened insulin resistance in diet-induced obese mice. These changes were associated with the reduced muscle weight and compromised Akt signaling activation. Importantly, Ip3r1 deletion in adipocytes protected mice from diet-induced obesity and glucose intolerance, mainly due to the enhanced lipolysis and AMPK signaling pathway in the visceral fat. In conclusion, our study demonstrates that IP3R1 in skeletal muscle and adipocytes exerts divergent effects on systemic glucose homeostasis, and characterizes adipocyte IP3R1 as a promising target for treating obesity and type 2 diabetes.

Dietary Valine/Isoleucine Ratio Impact Carcass Characteristics, Meat Edible Quality and Nutritional Values in Finishing Crossbred Duroc × Landrace × Yorkshire Pigs With Different Slaughter Weights.

The aim of this study was to investigate effects of dietary ratio of valine to isoleucine [R(V/I)] on carcass characteristics and meat quality of finishing pigs and whether slaughter weight influence the effect. We carried out a 2 × 3 factorial trial with two slaughter weight (105 vs. 130 kg) and three R(V/I) (0.58, 1.23, and 2.60 at 75-100 kg body weight, and 0.70, 1.24, and 2.39 at 100-135 kg body weight for L-, N- and H-R (V/I), respectively). Data show that increasing slaughter weight significantly increased meat color (a*45 min and b*45 min), drip loss and shear force (P < 0.05). Meanwhile, increasing slaughter weight reduced sarcomere length, the proportion of protein-bound water, and most kinds of muscular total amino acid contents except for tryptophan and arginine, while increased contents of muscular free lysine, tryptophan, leucine, isoleucine, valine, alanine, and arginine in the M. longissimus thoracis (P < 0.05). Health lipid indices based on fatty acid composition of intramuscular lipid were improved as the slaughter weight increased (P < 0.05). Notably, pigs received N-R (V/I) diet improved carcass traits in terms of thinner backfat thickness and higher fat-free lean index, as well as increased meat flavor-contributing amino acids at the cost of reduced intramuscular fat content and increased shear force of cooked meat compared with the pigs fed L-R (V/I) and H-R(V/I) diets (P < 0.05). H-R (V/I) diet decreased ultimate pH value and sarcomere length of the skeletal muscle but increased the proportion of free water (T 23), consequently, increased drip loss and cooking loss of fresh meat in pigs (P < 0.05). In conclusion, both slaughter weight and dietary ratio of valine to isoleucine exerted significant impacts on carcass characteristics, meat quality and nutrition values. In particular, carcass traits and meat color of lighter pigs were more susceptible to the influence of dietary R (V/I) relative to heavier pigs.

The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation.

Fufang Zhenshu Tiaozhi (FTZ) has been widely used in clinical practice and proven to be effective against aging-induced osteoporosis in mice. This study aimed to explore the mechanism of FTZ against osteoclastogenesis and ovariectomized-induced (OVX) bone loss through the network pharmacology approach. The ingredients of FTZ were collected from the previous UPLC results, and their putative targets were obtained through multiple databases. Differentially expressed genes (DEGs) during osteoclastogenesis were identified through multi-microarrays analysis. The common genes between FTZ targets and DEGs were used to perform enrichment analyses through the clusterProfier package. The affinity between all FTZ compounds and enriched genes was validated by molecular docking. The effects of FTZ on osteoclastogenesis and bone resorption were evaluated by TRAP staining, bone resorption assay and RT-qPCR in vitro, while its effects on bone loss by ELISA and Micro-CT in vivo. Enrichment analyses indicated that the inhibitory effects of FTZ may primarily involve the regulation of inflammation, osteoclastogenesis, as well as TNF-α signaling pathway. 130 pairs docking results confirmed FTZ ingredients have good binding activities with TNF-α pathway enriched genes. FTZ treatment significantly reduced TRAP, TNF-α, IL-6 serum levels and increased bone volume in OVX mice. Consistently, in vitro experiments revealed that FTZ-containing serum significantly inhibited osteoclast differentiation, bone resorption, and osteoclast related mRNA expression. This study revealed the candidate targets of FTZ and its potential mechanism in inhibiting osteoclastogenesis and bone loss induced by OVX, which will pave the way for the application of FTZ in the postmenopausal osteoporosis treatment.

Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease.

Vitamin D is one of the most important nutrients required by the human body. It is a steroid hormone that plays an important role in regulating calcium and phosphorus metabolism, and bone health. Epidemiological studies have revealed a close correlation between vitamin D and many common chronic diseases. Additionally, vitamin D has recently been shown to act as an immunomodulatory hormone, and, accordingly, vitamin D deficiency was uncovered as a risk factor for autoimmune thyroid diseases, although the underlying mechanisms are still unknown. It is therefore necessary to disclose the role and mechanism of action of vitamin D in the occurrence and development of autoimmune thyroid diseases. This knowledge will help design intervention and early treatment strategies for patients with autoimmune thyroid diseases who present with low levels of vitamin D.

Dietary Malic Acid Supplementation Induces Skeletal Muscle Fiber-Type Transition of Weaned Piglets and Further Improves Meat Quality of Finishing Pigs.

The aim of this study was to investigate effects of dietary malic acid supplementation on skeletal muscle fiber-type transition during nursery period and the subsequent meat quality of finishing pigs. Results showed that malic acid supplementation for 28 days increased oxidative fiber percentage of weaned piglets, accompanied by the increased aerobic oxidation in serum and longissimus thoracis (LT) muscle. Additionally, activities of total antioxidant capacity and glutathione peroxidase in serum were increased. Moreover, dietary malic acid supplementation during nursery period tended to increase pH24h and significantly decreased drip loss in LT muscle of finishing pigs. The content of total saturated fatty acid (SFA) and total monounsaturated fatty acid in LT muscle was significantly decreased, whereas the ratio of polyunsaturated fatty acid to SFA tended to increase. Together, dietary malic acid supplementation during nursery period can effectively increase antioxidant capacity and oxidative fibers percentage of weaned piglets, and further improve water holding capacity and nutritional values of pork in finishing pigs.

The guiding role of bone metabolism test in osteoporosis treatment.

Osteoporosis (OP) and osteoporotic fractures are becoming a serious health care issue in the world. Calcium and vitamin D are the basic treatment for osteoporosis. Nonetheless, they do not effectively reduce the incidences of fracture. Currently approved treatments for osteoporosis include selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, teriparatide, calcitonin and others. However, the appearance of some adverse effects including atypical fracture and breast cancer has limited long-term treatments above mentioned. Therefore, treatment decision should be made on an individual basis, taking into account the relative benefits and risks in different patients. Bone metabolism test helps to assess the patient's condition, which may ultimately lead to therapeutic options and better clinical outcomes.

Clinical and next-generation sequencing findings in a Chinese family exhibiting severe familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a rare hereditary retinal disorder characterized by the premature arrest of vascularization in the peripheral retina. The aim of the present study was to characterize the clinical presentations of a Chinese family affected by bilateral severe FEVR, and to identify the underlying genetic variations. One family that presented with bilateral FEVR was recruited for this study. Comprehensive ophthalmic examinations, including best­corrected visual acuity, slit­lamp examination, fundus photography, fundus fluorescein angiography imaging and electroretinogram were performed. Genomic DNA was extracted from leukocytes of the peripheral blood collected from the affected and unaffected family members, as well as 200 unrelated control subjects from the same population. Next­generation sequencing of the candidate genes associated with ocular diseases was performed, and the identified mutations were validated by conventional polymerase chain reaction­based sequencing. The functional effects of the mutations were analyzed by polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT). One heterozygous ATP binding cassette subfamily A member 4 (ABCA4) c.5693G>A (p.R1898H) mutation in exon 40 and one heterozygous LDL receptor related protein 5 (LRP5) c.260T>G (p.I87S) mutation in exon 2 were identified in this family. To the best of our knowledge, the ABCA4 c.5693G>A (p.R1898H) mutation has not been reported in FEVR, and the LRP5 c.260T>G (p.I87S) mutation is a novel mutation. PolyPhen and SIFT predicted that the amino acid substitution R1898H in protein ABCA4 is benign, whereas the amino acid substitution I87S in protein LRP5 is damaging. A single nucleotide polymorphism c.266A>G (p.Q89R, rs41494349) was identified in exon 2 of LRP5. These findings expand the mutation spectrums of ABCA4 and LRP5, and will be valuable for genetic counseling and development of therapeutic interventions for patients with FEVR.

Genetic variations in Bestrophin­1 and associated clinical findings in two Chinese patients with juvenile­onset and adult­onset best vitelliform macular dystrophy.

Best vitelliform macular dystrophy (BVMD) is a hereditary retinal disease characterized by the bilateral accumulation of large egg yolk­like lesions in the sub­retinal and sub­retinal pigment epithelium spaces. Macular degeneration in BVMD can begin in childhood or adulthood. The variation in the age of onset is not clearly understood. The present study characterized the clinical characteristics of two Chinese patients with either juvenile­onset BVMD or adult­onset BVMD and investigated the underlying genetic variations. A 16­year­old male (Patient 1) was diagnosed with juvenile­onset BVMD and a 43­year­old female (Patient 2) was diagnosed with adult­onset BVMD. Comprehensive ophthalmic examinations were performed, including best­corrected visual acuity, intraocular pressure, slit­lamp examination, fundus photography, optical coherence tomography, fundus fluorescein angiography imaging and Espion electrophysiology. Genomic DNA was extracted from peripheral blood leukocytes collected from these patients, their family members, and 200 unrelated subjects within in the same population. The 11 exons of the bestrophin­1 (BEST1) gene were amplified by polymerase chain reaction and directly sequenced. Both patients presented lesions in the macular area. In Patient 1, a heterozygous mutation c.903T>G (p.D301E) in exon 8 of the BEST1 gene was identified. This mutation was not present in any of the unaffected family members or the normal controls. Polymorphism phenotyping and the sorting intolerant from tolerant algorithm predicted that the amino acid substitution D301E in bestrophin­1 protein was damaging. In Patient 2, a single nucleotide polymorphism c.1608C>T (p.T536T) in exon 10 of the BEST1 gene was identified. These findings expand the spectrum of BEST1 genetic variation and will be valuable for genetic counseling and the development of therapeutic interventions for patients with BVMD.

[The change of transforming growth factor-beta1 in nonproliferation diabetic retinopathy].

PURPOSE: To evaluate the relationship between the level of transforming growth factor-beta1 (TGF-beta1) in serum of patients with nonproliferation diabetic retinopathy and the severity of this retinopathy, and to find out a new method for early intervention of diabetic retinopathy. METHOD: TGF-beta1 in serum was measured in the three groups as following: group DR containing the patients with nonproliferation diabetic retinopathy identified by funds fluorescein angiography, group DM consisting of diabetic without diabetic retinopathy, and group C containing healthy people, and analysed statistically. Then the patients with diabetic retinopathy were divided into three subgroups based on the phase of retinopathy: DR1, DR2, DR3, which results were also analysed statistically. RESULT: The level of TGF-beta1 in serum had no significant difference between the group DM and group C, and the level of the group DR was higher than group DM or the group C significantly. The level of the group DR1 was lower than the group DR2 DR3 significantly. CONCLUSION: In patients with nonproliferation diabetic retinopathy, the level of TGF-beta1, in serum is increased, and can reflect the severity of diabetic retinopathy. The level of TGF-beta1 in serum can also indicate the time of intervention to a certain extent.