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PURPOSE OF REVIEW: Traditional Chinese Medicine has a unique system to diagnose and treat bone diseases with symptoms similar to those of osteoporosis. Sambucus williamsii Hance (SWH), a folk medicine in northern part of China for fractures healing and pain alleviation, has been demonstrated to exert bone anabolic effects in ovariectomized (OVX) rat and mice models in our previous studies. Lignans were identified to be the main bioactive fractions of SWH. However, pharmacokinetics study showed that the levels of lignan were too low to be detected in rat serum even upon taking 15 times of the effective dose of lignan-rich fraction from SWH. We hypothesize that lignans from SWH might exert its bone protective effect via the gut microbiome. RECENT FINDINGS: Our study revealed that the lignan-rich fraction of SWH did not influence the diversity of gut microbiota in OVX rats, but significantly increased the abundance of a few phyla, in particular, the restoration of the abundance of several genera that was directly correlated with bone mineral density (BMD). In addition, a subsequent metabolomic study indicated that serotonin, a neurotransmitter synthesized in the intestine and influenced by gut microbiota, may be involved in mediating the bone protective action of the lignans. Gut-derived serotonin is thought to inhibit bone growth. Based on this finding, several inhibitors that suppressed the synthesis of serotonin were identified from the lignans of SWH. Our studies suggested that microbiome is an indispensable factor for lignans derived from S. willimasii to exert bone beneficial effects.

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Cornea is the major barrier to drug delivery to the eye, which results in low bioavailability and poor efficacy of topical eye treatment. In this work, we first select cornea-binding aptamers using tissue-SELEX on pig cornea. The top two abundant aptamers, Cornea-S1 and Cornea-S2, could bind to pig cornea, and their K d values to human corneal epithelial cells (HCECs) were 361 and 174 nм, respectively. Aptamer-functionalized liposomes loaded with cyclosporine A (CsA) were developed as a treatment for dry eye diseases. The K d of Cornea-S1- or Cornea-S2-functionalized liposomes reduces to 1.2 and 15.1 nм, respectively, due to polyvalent binding. In HCECs, Cornea-S1 or Cornea-S2 enhanced liposome uptake within 15 min and extended retention to 24 h. Aptamer CsA liposomes achieved similar anti-inflammatory and tight junction modulation effects with ten times less CsA than a free drug. In a rabbit dry eye disease model, Cornea-S1 CsA liposomes demonstrated equivalence in sustaining corneal integrity and tear break-up time when compared to commercial CsA eye drops while utilizing a lower dosage of CsA. The aptamers obtained from cornea-SELEX can serve as a general ligand for ocular drug delivery, suggesting a promising avenue for the treatment of various eye diseases and even other diseases.

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BACKGROUND AND PURPOSE: Icariin, an 8-prenylated flavonoid glycoside, is an anabolic agent that could exert rapid estrogenic actions via ligand-independent activation of estrogen receptor alpha (ERα) in osteoblastic cells to promote osteogenesis. However, relatively little is known about its direct cellular target, its protective effects, and cell adhesion activities in bone marrow stromal cells (BMSCs) against microgravity. In the present study, the effects of icariin on osteogenesis and cell adhesion under microgravity were examined with the involvement of integrin receptor α5ß1, connexin 43, and CAMs. STUDY DESIGN AND METHODS: Icariin was orally administered to 6-month-old ovariectomized (OVX) Sprague-Dawley (SD) rats for 3 months through daily intake of phytoestrogen-free rodent diets containing icariin at 2 different dosages (50 and 500 ppm). BMSCs were harvested for experiments and RNA-sequencing analysis to examine the mechanism of action of icariin and its direct cellular target in stimulating osteogenesis. RESULTS: The results revealed that icariin induced the expression of cell adhesion molecules (CAMs) and protected against microgravity-induced disruption of actin cytoskeleton and the loss of osteogenic activities in BMSCs through the activation of connexin-43 (Cx43) and Ras homolog family member A (RhoA) and Rac family small GTPase 1 (Rac1)-mediated signaling pathways. Computerized molecular docking techniques and the competitive solid-phase binding ELISA assay confirmed that icariin could be a direct ligand of integrin alpha 5 beta 1 (α5ß1), and it could also increase the protein expression of integrin α5ß1 for mechanosensing. CONCLUSION: Our findings suggest that icariin could directly activate cell adhesion signaling by binding to integrin α5ß1, which opens up new avenues for the development of integrin α5ß1 ligand as an agent to protect against unloading-induced bone loss.

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Nanozymes, characterized by their nanoscale size and enzyme-like catalytic activities, exhibit diverse therapeutic potentials, including anti-oxidative, anti-inflammatory, anti-microbial, and anti-angiogenic effects. These properties make them highly valuable in nanomedicine, particularly ocular therapy, bypassing the need for systemic delivery. Nanozymes show significant promise in tackling multi-factored ocular diseases, particularly those influenced by oxidation and inflammation, like dry eye disease, and age-related macular degeneration. Their small size, coupled with their ease of modification and integration into soft materials, facilitates the effective penetration of ocular barriers, thereby enabling targeted or prolonged therapy within the eye. This review is dedicated to exploring ocular diseases that are intricately linked to oxidation and inflammation, shedding light on the role of nanozymes in managing these conditions. Additionally, recent studies elucidating advanced applications of nanozymes in ocular therapeutics, along with their integration with soft materials for disease management, are discussed. Finally, this review outlines directions for future investigations aimed at bridging the gap between nanozyme research and clinical applications.

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Drug delivery is a key component of nanomedicine, and conventional delivery relies on the adsorption or encapsulation of drug molecules to a nanomaterial. Many delivery vehicles contain metal ions, such as metal-organic frameworks, metal oxides, transition metal dichalcogenides, MXene, and noble metal nanoparticles. These materials have a high metal content and pose potential long-term toxicity concerns leading to difficulties for clinical approval. In this review, recent developments are summarized in the use of drug molecules as ligands for metal coordination forming various nanomaterials and soft materials. In these cases, the drug-to-metal ratio is much higher than conventional adsorption-based strategies. The drug molecules are divided into small-molecule drugs, nucleic acids, and proteins. The formed hybrid materials mainly include nanoparticles and hydrogels, upon which targeting ligands can be grafted to improve efficacy and further decrease toxicity. The application of these materials for addressing cancer, viral infection, bacterial infection inflammatory bowel disease, and bone diseases is reviewed. In the end, some future directions are discussed from fundamental research, materials science, and medicine.

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Changes in an individual's digestive system, hormones, senses of smell and taste, and energy requirement accompanying aging could lead to impaired appetite, but older adults may not notice their risk of nutrient deficiency. When assessing the dietary intake of older adults, it was found that they had more difficulties with short-term recall and open-ended recall and would experience greater fatigue and frustration when compared to younger individuals when completing a lengthy questionnaire. There is a need to develop a brief dietary assessment tool to examine the nutritional needs of older adults. In this study, we aimed to assess the diet of Hong Kong older adults using the short FFQ and examine its reproducibility and relative validity as a dietary assessment tool. Dietary data of 198 older adults were collected via FFQs and three-day dietary records. Correlation analyses, cross-tabulation, one-sample t-tests, and linear regression analyses were used to evaluate the relative validity of the short FFQ. In general, the short FFQ was accurate in assessing the intake of phosphorus, water, grains, and wine, as shown by a significant correlation (>0.7) between values reported in the FFQs and dietary records; good agreement (more than 50% of observations belonged to the same quartile) and insignificant differences detected with the one-sample t-tests and linear regression analyses were observed for the above four variables. Additionally, the intake of proteins, carbohydrates, total fat, magnesium, and eggs in terms of the values reported in the FFQs and dietary records showed good agreement.

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Oleanolic acid (OA) is previously shown to exert bone protective effects in aged animals. However, its role in regulating osteoblastic vitamin D bioactivation, which is one of major causes of age-related bone loss, remains unclear. Our results revealed that treatment of OA significantly increased skeletal CYP27B1 expression and circulating 1,25(OH)2D3 in ovariectomized mice (p <0.01). Moreover, OA upregulated CYP27B1 protein expression and activity, as well as the vitamin D-responsive bone markers alkaline phosphatase (ALP) activity and osteopontin (OPN) protein expression, in human osteoblast-like MG-63 cells (p<0.05). CYP27B1 expression increased along with the osteoblastic differentiation of human bone marrow derived mesenchymal stem cells (hMSCs). CYP27B1 expression and cellular 1,25(OH)2D3 production were further potentiated by OA in cells at mature osteogenic stages. Notably, our study suggested that the osteogenic actions of OA were CYP27B1 dependent. In summary, the bone protective effects of OA were associated with the induction of CYP27B1 activity and expression in bone tissues and osteoblastic lineages. Hence, OA might be a potential approach for management of age-related bone loss.

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Traditional Chinese Medicine has a long history in ophthalmology in China. Over 250 kinds of Traditional Chinese Medicine have been recorded in ancient books for the management of eye diseases, which may provide an alternative or supplement to current ocular therapies. However, the core holistic philosophy of Traditional Chinese Medicine that makes it attractive can also hinder its understanding from a scientific perspective - in particular, determining true cause and effect. This review focused on how Traditional Chinese Medicine could be applied to two prevalent ocular diseases, glaucoma, and cataract. The literature on preclinical and clinical studies in both English and Chinese on the use of Traditional Chinese Medicine to treat these two diseases was reviewed. The pharmacological effects, safety profile, and drug-herb interaction of selected herbal formulas were also investigated. Finally, key considerations for conducting future Traditional Chinese Medicine studies are discussed.

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Among the various targeting ligands for drug delivery, aptamers have attracted much interest in recent years because of their smaller size compared to antibodies, ease of modification, and better batch-to-batch consistency. In addition, aptamers can be selected to target both known and even unknown cell surface biomarkers. For drug loading, liposomes are the most successful vehicle and many FDA-approved formulations are based on liposomes. In this paper, aptamer-functionalized liposomes for targeted drug delivery are reviewed. We begin with the description of related aptamers selection, followed by methods to conjugate aptamers to liposomes and the fate of such conjugates in vivo. Then a few examples of applications are reviewed. In addition to intravenous injection for systemic delivery and hoping to achieve accumulation at target sites, for certain applications, it is also possible to have aptamer/liposome conjugates applied directly at the target tissue such as intratumor injection and dropping on the surface of the eye by adhering to the cornea. While previous reviews have focused on cancer therapy, the current review mainly covers other applications in the last four years. Finally, this article discusses potential issues of aptamer targeting and some future research opportunities.

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Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

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Icariin, a flavonoid glycoside derived from Epimedium brevicornum Maxim, exerts bone protective effects via estrogen receptors (ERs). This study aimed to investigate the role of ER-α66, ER-α36, and GPER in bone metabolism in osteoblasts following treatment with icariin. Human osteoblastic MG-63 cells and osteoblast-specific ER-α66 knockout mice were employed. The ERs crosstalk in the estrogenic action of icariin was evaluated in ER-α66-negative human embryonic kidney HEK293 cells. Icariin, like E2, regulated ER-α36 and GPER protein expression in osteoblasts by downregulating them and upregulating ER-α66. ER-α36 and GPER suppressed the actions of icariin and E2 in bone metabolism. However, the in vivo administration of E2 (2 mg/kg/day) or icariin (300 mg/kg/day) restored bone conditions in KO osteoblasts. ER-α36 and GPER expression increased significantly and rapidly activated and translocated in KO osteoblasts after treatment with E2 or icariin. ER-α36 overexpression in KO osteoblasts further promoted the OPG/RANKL ratio induced by E2 or icariin treatment. This study showed icariin and E2 elicit rapid estrogenic responses in bone through recruiting ER-α66, ER-α36, and GPER. Notably, in osteoblasts lacking ER-α66, ER-α36, and GPER mediate the estrogenic effects of icariin and E2, while in intact osteoblasts, ER-α36 and GPER act as negative regulators of ER-α66.

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Traditional eye drops are convenient to use; however, their effectiveness is limited by their poor retention time and bioavailability in the eyes due to ocular barriers. Therefore, strategies to enhance ocular drug delivery are required. Herein, we constructed a mucin-1 aptamer-functionalized liposome and loaded it with cyclosporin A, a common ocular drug in eye drops used to treat dry eye diseases (DED). Drug encapsulation slightly reduced the liposome size without changing the surface potential of liposomes. Approximately 90% of the cholesterol-modified aptamers were inserted to the liposomes. We evaluated the cytotoxicity, anti-inflammatory effects, cell permeability regulation, and retention time of liposomes in human corneal epithelial cells under dry eye conditions. These results suggest that the aptamer-functionalized liposomes are more efficient as nanocarriers than non-functionalized liposomes and drug-free liposomes. They restore inflammation levels by 1-fold and remain in the cells for up to 24 h. An in vivo study was also performed in a rat DED model, which demonstrated the efficacy of aptamer-functionalized liposomes in restoring tear production and corneal integrity. The present study demonstrated the capability of aptamer-functionalized liposomes in the delivery of ocular drugs for the management of ocular diseases.

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BACKGROUND: The health benefits of breastfeeding are partly contributed by human milk oligosaccharides (HMOs), but there is limited data on breast milk (BM) HMO composition in Chinese. OBJECTIVE: This study investigated the association between early-life HMO intake and allergy occurrence in Chinese children. METHODS: 103 healthy Chinese pregnant women regardless of allergy history were recruited into this birth cohort. Their babies were followed until 24 months old. Concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), -sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) in BM collected at 1-month postpartum were measured by liquid chromatography-mass spectrometry. The associations between these HMOs and allergy occurrence by 24 months were analyzed by multivariate regression analyses. RESULTS: Twenty-nine percent and 19% of participants had eczema at 12 and 24 months old respectively. Eighty BM samples were analyzed, with 2'-FL being the most abundant HMO (median 1447 ppm, interquartile range [IQR] 291-1906 ppm), and median (IQR) levels of LNnT, 6'-SL and 3'-SL in ppm were 738 (580-950), 20.5 (12.7-38.8) and 23.0 (17.8-27.6) respectively. Participants with eczema by 24 months consumed BM with higher 2'-FL concentration at 1-month (P = 0.008), and also lower 6'-SL concentration in exclusively breastfed infants (P = 0.012) but higher 6'-SL concentration for those with mixed feeding at 1 month (P = 0.043). Food allergic children at 12 months consumed BM with higher 2'-FL concentrations at 1 month (P = 0.048). CONCLUSIONS: BM 2'-FL concentration is higher in children who develops eczema by 24 months and food allergy during infancy. The relationship for 6'-SL is divergent depending on mode of feeding in infants.

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BACKGROUND: Skin prick testing and serological identification of allergen specific immunoglobulin E (spIgE) are standard tests for allergic rhinitis but can only identify systemic responses. In contrast, nasal allergen challenge (NAC), directly assess localized nasal mucosal reactivity, but is time consuming. Identification of spIgE from nasal brushings (nasal spIgE) is an alternative technique. OBJECTIVE: This study aimed to determine the diagnostic performance of nasal spIgE compared to NAC in order predict house dust mite (HDM) driven AR. METHODS: A diagnostic cross-sectional study involving adult rhinitis patients was performed. Sensitization to HDM allergens (Dermatophagoides pteronyssinus (DP), Dermatophagoides farina (DF) were assessed serologically and/or skin prick test, nasal brushing and NAC. Patients with both positive systemic test and NAC were defined to have HDM driven AR, while patients with a positive systemic test and negative NAC were defined to have non-clinically relevant HDM sensitization. The performance of nasal spIgE to predict positive NAC was determined using the receiver operating curve. The chosen cut-off was then used to predict HDM driven AR among those with positive systemic test. RESULTS: 118 patients (29.42 ± 9.32 years, 61.9% female) were included. Nasal spIgE was predictive of positive NAC (AUC 0.93, 95%CI: 0.88-0.98, p < 0.01). Among those with positive systemic test, the cut-off value of >0.14 kUA/L was able to predict HDM AR from incidental HDM sensitization with 92% sensitivity and 86% specificity. CONCLUSIONS: Nasal spIgE is comparable to NAC. A cut-off value of >0.14 kUA/L identifies HDM-driven AR from incidental sensitization among patients with positive systemic tests for allergy.

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ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a traditional Chinese medicine that has been used for tonifying the kidney and liver for decades. AIM OF THE STUDY: This study aimed to explore and identify polysaccharides from FLL and elucidate its protective effect against renal fibrosis. MATERIALS AND METHODS: Polysaccharides were extracted and isolated from FLL. The purified fraction was identified by serial phytochemical work, such as gel-permeation chromatography, ion chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance. Mice with unilateral ureteral obstruction (UUO) were applied as a renal fibrosis model. The male UUO mice were pretreated with heteropolysaccharide (Poly) 1 week prior to surgery and continuously treated for 7 days after the operation. Renal fibrosis was assessed by Periodic Acid-Schiff (PAS) staining and Masson's trichrome staining in paraffin-embedded slides. The murine mesangial cells SV40-MES13 upon angiotensin II (Ang II) treatment were developed as an in vitro fibrotic model. The cells were treated by Poly in the presence of Ang II. Molecular expression was detected by RT-PCR, immunoblotting, and immunofluorescence staining. RESULTS: We identified a heteropolysaccharide composed of arabinose and galactose (molar ratio, 0.73:0.27) with a predicted chemical structure characterized by a backbone composed of 1,5-α-Araf, 1,3,5-α-Araf, 1,6-α-Galp, and 1,3,6-ß-Galp and side chains comprised of T-α-Araf, T-α-Arap, and 1,3-α-Araf. Pretreatment of UUO mice with Poly effectively alleviated glomerulosclerosis and tubulointerstitial fibrosis. Moreover, Poly pretreatment down-regulated the expression of extracellular matrix (ECM) protein fibronectin (FN), profibrotic factor VEGF, proinflammatory cytokines MCP-1 and Rantes in the obstructed kidney. Similarly, the incubation of SV40-MES13 cells with Poly significantly inhibited Ang II-induced elevation in accumulation and expression level of FN and attenuated Ang II-evoked up-regulation in protein expression of MCP-1 and Rantes. CONCLUSIONS: Our study isolated and identified a naturally occurring heteropolysaccharide in FLL and revealed its potential in protecting the kidneys from fibrosis.

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Postmenopausal osteoporosis is a significant threat to human health globally. Genistein, a soy-derived isoflavone, is regarded as a promising anti-osteoporosis drug with the effects of promoting osteoblastogenesis and suppressing osteoclastogenesis. However, its oral bioavailability (6.8%) is limited by water solubility, intestinal permeability, and biotransformation. Fortunately, 8-prenelylated genistein (8PG), a derivative of genistein found in Erythrina Variegate, presented excellent predicted oral bioavailability (51.64%) with an improved osteoblastogenesis effect, although its effects on osteoclastogenesis and intestinal biotransformation were still unclear. In this study, an in vitro microbial transformation platform and UPLC-QTOF/MS analysis method were developed to explore the functional metabolites of 8PG. RANKL-induced RAW264.7 cells were utilized to evaluate the effects of 8PG on osteoclastogenesis. Our results showed that genistein was transformed into dihydrogenistein and 5-hydroxy equol, while 8PG metabolites were undetectable under the same conditions. The 8PG (10-6 M) was more potent in inhibiting osteoclastogenesis than genistein (10-5 M) and it down-regulated NFATC1, cSRC, MMP-9 and Cathepsin K. It was concluded that 8-prenyl plays an important role in influencing the osteoclast activity and intestinal biotransformation of 8PG, which provides evidence supporting the further development of 8PG as a good anti-osteoporosis agent.

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Our previous study revealed that the bone anabolic effects of the lignan-rich fraction (SWCA) from Sambucus williamsii Hance was involved in modulating the metabolism of tryptophan in vivo and inhibiting serotonin (5-HT) synthesis in vitro. This study aimed to determine how SWCA modulates bone metabolism via serotonin in vivo. The effects of SWCA were evaluated by using 4-month-old Sprague-Dawley (SD) ovariectomized rats. The serum levels of 5-HT and kynurenine, the protein expressions of tryptophan hydroxylase 1 (TPH-1) and TPH-2, the genes and proteins related to the 5-HT signaling pathway as well as gut microbiota composition were determined. SWCA treatment alleviated bone loss and decreased serum levels of serotonin, which was negatively related to bone mineral density (BMD) in rats. It suppressed the protein expression of TPH-1 in the colon, and reversed the gene and protein expressions of FOXO1 and ATF4 in the femur in OVX rats, while it did not affect the TPH-2 protein expression in the cortex. SWCA treatment escalated the relative abundance of Antinobacteria and modulated several genera relating to BMD. These findings verified that the bone protective effects of lignans were mediated by serotonin, and provided evidence that lignans might be a good source of TPH-1 inhibitors.

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Introduction: In postmenopausal women, vitamin D deficiency (as defined by the circulating level of 25(OH)D being below 20 ng/ml (50 nmol/L)) is a regular occurrence. The effect of vitamin D supplementation on the muscle function of postmenopausal women has been controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines and summarizes the effects of vitamin D supplementation on the muscular strength and mobility of postmenopausal women. Methods: RCTs that met the inclusion criteria for this study were identified by searching PubMed, EMBASE, and the Cochrane Library. Postmenopausal women who were included in the study were exposed to RCTs assessing the effectiveness of vitamin D supplements. Meta-analysis data were extracted by two independent reviewers and screened for methodological quality. RCTs that did not meet the minimum requirement for assessment were excluded. In the meta-analysis, the effect size (weighted mean differences, WMD) of handgrip strength (HGS) and timed-up and go test (TUG) with a 95% confidence interval (CI) was obtained to compare reported results across the included RCTs. Results: A total of 19 trials were included in this systematic review, among which 13 trials were eligible for the meta-analysis. In the 13 included studies, supplementing with vitamin D produced a weighted mean difference of 0.876 kg (95% CI = 0.180 to 1.571, P = 0.014, I2 = 68.5%) for HGS, a measurement of muscle strength. However, an insignificant decrease of 0.044 s was observed after analyzing the TUG (95% CI = -0.979 to 0.892, P = 0.927, I2 = 95%). According to subgroup analysis, vitamin D supplementation increased HGS in patients over the age of 60 (P = 0.001), in those without calcium supplementation (P = 0.032), and in those whose baseline vitamin D level was greater than 75 nmol/L (30 ng/ml) (P = 0.003). Conclusions: Taking into account the studies in this systematic review, vitamin D supplementation improved muscle strength in postmenopausal women. However, an insignificant result was demonstrated in terms of mobility after vitamin D supplementation.

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Carotenoids and vitamin A are nutrients crucial to infants' development. To date, there is limited data on their availability in breastmilk and the associated dietary factors, especially in Hong Kong, where people follow a westernized Chinese diet. This study determined the selected breastmilk's carotenoid and vitamin A (retinol) contents by ultraperformance liquid chromatography with photodiode detection (UPLC-PDA) and the dietary intakes by three-day food records in 87 Hong Kong lactating mothers, who were grouped into tertiles based on their daily carotenoid intake. Low vitamin A intake (530.2 ± 34.2 µg RAE/day) and breastmilk retinol level (1013.4 ± 36.8 nmol/L) were reported in our participants, suggesting a poor vitamin A status of the lactating participants having relatively higher socioeconomic status in Hong Kong. Mothers in the highest tertile (T3) had higher breastmilk carotenoid levels than those in the lowest (T1) (p < 0.05). There were significant associations between maternal carotenoid intakes and breastmilk lutein levels in the linear regression models (p < 0.05) regardless of dietary supplement intake. Furthermore, maternal dark green vegetable intakes were associated with breastmilk retinol, lutein, and ß-carotene levels. These findings can serve as dietary references for lactating mothers to enhance breastmilk carotenoid and vitamin A contents for the benefits of child growth and development.

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Our previous study demonstrated that the bone protective actions of herbal medicine Rhizoma Drynariae (Gusuibu, RD) were mainly mediated by flavonoid phytoestrogens via estrogen receptors, raising concerns about the safety of using RD as it may induce estrogen-like risk-benefit profile and interact with other ER ligands, such as selective estrogen receptor modulators (SERMs), when coadministered. The present study evaluated the estrogenic activities of RD and its potential interaction with tamoxifen, a SERM, in estrogen-sensitive tissues by using mature ovariectomized (OVX) rats and ER-positive cells. Similar to but weaker than tamoxifen, RD at its clinical dose dramatically ameliorated OVX-induced changes in bone and dopamine metabolism-related markers in OVX rats. However, tamoxifen, but not RD, induced uterotrophic effects. No significant alteration in mammary gland was observed in OVX rats treated with RD, which was different from the inhibitory actions of tamoxifen. The two-way ANOVA results indicated the interactions between RD and tamoxifen in the bone, brain, and uterus of OVX rats while RD did not alter their responses to tamoxifen. Our results demonstrate that RD selectively exerts estrogenic actions in a different manner from tamoxifen. Moreover, RD interacts with tamoxifen without altering its effects in OVX rats.

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