Strontium and Zinc Co-Doped Mesoporous Bioactive Glass Nanoparticles for Potential Use in Bone Tissue Engineering Applications.

Mesoporous bioactive glass nanoparticles (MBGNs) have attracted significant attention as multifunctional nanocarriers for various applications in both hard and soft tissue engineering. In this study, multifunctional strontium (Sr)- and zinc (Zn)-containing MBGNs were successfully synthesized via the microemulsion-assisted sol-gel method combined with a cationic surfactant (cetyltrimethylammonium bromide, CTAB). Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs exhibited spherical shapes in the nanoscale range of 100 ± 20 nm with a mesoporous structure. Sr and Zn were co-substituted in MBGNs (60SiO2-40CaO) to induce osteogenic potential and antibacterial properties without altering their size, morphology, negative surface charge, amorphous nature, mesoporous structure, and pore size. The synthesized MBGNs facilitated bioactivity by promoting the formation of an apatite-like layer on the surface of the particles after immersion in Simulated Body Fluid (SBF). The effect of the particles on the metabolic activity of human mesenchymal stem cells was concentration-dependent. The hMSCs exposed to Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs at 200 µg/mL enhanced calcium deposition and osteogenic differentiation without osteogenic supplements. Moreover, the cellular uptake and internalization of Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs in hMSCs were observed. These novel particles, which exhibited multiple functionalities, including promoting bone regeneration, delivering therapeutic ions intracellularly, and inhibiting the growth of Staphylococcus aureus and Escherichia coli, are potential nanocarriers for bone regeneration applications.

Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma.

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

The effect of respiratory muscle training on children and adolescents with cystic fibrosis: a systematic review and meta-analysis.

BACKGROUND: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. METHODS: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. RESULTS: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. CONCLUSIONS: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. TRIAL REGISTRATION: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.

Unleashing the potential: integrating nano-delivery systems with traditional Chinese medicine.

This review explores the potential of integrating nano-delivery systems with traditional Chinese herbal medicine, acupuncture, and Chinese medical theory. It highlights the intersections and potential of nano-delivery systems in enhancing the effectiveness of traditional herbal medicine and acupuncture treatments. In addition, it discusses how the integration of nano-delivery systems with Chinese medical theory can modernize herbal medicine and make it more readily accessible on a global scale. Finally, it analyzes the challenges and future directions in this field.

Complementary and alternative medicine: A narrative review of nutritional approaches for cancer-related fatigue.

Cancer-related fatigue (CRF) is a common symptom among patients with cancer, with a prevalence of >49%. CRF significantly affects the quality of life of patients and may also affect their overall survival. Pharmacological interventions serve as a last resort after carefully weighing the risks and benefits, with limited benefits for patients, many side effects, and adverse reactions. Compared to traditional medicine, nutritional approaches have fewer side effects, are highly accepted by patients, and do not affect the antitumor treatment of patients. Many studies have shown that nutritional approaches, as a form of complementary and alternative medicine, help improve the symptoms of CRF and the quality of life of patients. This study was designed to examine nutritional approaches to CRF and assess their effectiveness of nutritional approaches in improving CRF. We present an overview of clinical trials investigating nutritional approaches for CRF that have been published over the last 2 decades. A total of 33 records were obtained from 3 databases: Web of Science, MEDLINE, and PubMed. Some nutritional approaches, such as melatonin, PG2, and S-adenosyl-l-methionine, are potential options for CRF treatment. However, the trials included in the review varied widely in quality, most were weak in methodology, and there is currently insufficient evidence to conclude with certainty the effectiveness of nutritional approaches in reducing CRF. Therefore, the design and methods used in future complementary and alternative medicine trials should be more rigorous.

Rice husk ash based growing media impact on cucumber and melon growth and quality.

Rice husk, an agricultural waste from the rice industry, can cause serious environmental pollution if not properly managed. However, rice husk ash (RHA) has been found to have many positive properties, making it a potential replacement for non-renewable peat in soilless planting. Thus, this study investigated the impact of a RHA composite substrate on the growth, photosynthetic parameters, and fruit quality of cucumber (Yuyi longxiang variety) and melon (Yutian yangjiaomi variety). The RHA, peat, vermiculite, and perlite were blended in varying proportions, with the conventional seedling substrate (peat:vermiculite:perlite = 1:1:1 volume ratio) serving as the control (CK). All plants were cultivated in barrels filled with 10L of the mixed substrates. The results from this study found that RHA 40 (RHA:peat:vermiculite:perlite = 4:4:1:1 volume ratio) significantly enhanced substrate ventilation and positively influenced the stem diameter, root activity, seedling index, chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of cucumber and melon plants. Additionally, plant planted using RHA 40, the individual fruit weight of cucumber and melon found to increase by 34.62% and 21.67%, respectively, as compared to the control. Aside from that, both cucumber and melon fruits had significantly higher sucrose, total soluble sugar, vitamin C, and soluble protein levels. This subsequently improved the activity of sucrose synthase and sucrose phosphate synthase in both cucumber and melon. In conclusion, the RHA 40 found to best promote cucumber and melon plant growth, increase plant leaf photosynthesis, and improve cucumber and melon fruit quality, making it a suitable substrate formula for cucumber and melon cultivation in place of peat.

Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation.

OBJECTIVE: This study explores the mechanism of action of Danhongqing formula (DHQ), a compound-based Chinese medicine formula, in the treatment of cholestatic liver fibrosis. METHODS: In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout (Mdr2-/-) mice as an animal model of cholestatic liver fibrosis. DHQ was administered orally for 8 weeks, and its impact on cholestatic liver fibrosis was evaluated by assessing liver function, liver histopathology, and the expression of liver fibrosis-related proteins. Real-time polymerase chain reaction, Western blot, immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19 (H19) and signal transducer and activator of transcription 3 (STAT3) phosphorylation in the liver tissue of Mdr2-/- mice. In addition, cholangiocytes and hepatic stellate cells (HSCs) were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression. Cholangiocytes overexpressing H19 were constructed, and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation. The intervention effect of DHQ on these processes was also investigated. HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ. RESULTS: DHQ alleviated liver injury, ductular reaction, and fibrosis in Mdr2-/- mice, and inhibited H19 expression, STAT3 expression and STAT3 phosphorylation. This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19, inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium, and decreased the expression of activation markers in HSCs. The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation, and DHQ was able to successfully inhibit these effects. CONCLUSION: DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/- mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC, thereby suppressing cell activation. Please cite this article as: Li M, Zhou Y, Zhu H, Xu LM, Ping J. Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation. J Integr Med. 2024; 22(2): 188-198.

Protective effect of phenylpropionamides in the seed of Cannabis Sativa L. on Parkinson's disease through autophagy.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. As one of the major degradation pathways, autophagy plays a pivotal role in maintaining the effective turnover of proteins and damaged organelles in cells. Lewy bodies composed of α-synuclein (α-syn) abnormally aggregated in the substantia nigra are important pathological features of PD, and autophagy dysfunction is considered to be an important factor leading to abnormal aggregation of α-syn. Phenylpropionamides (PHS) in the seed of Cannabis sativa L. have a protective effect on neuroinflammation and antioxidant activity. However, the therapeutic role of PHS in PD is unclear. In this study, the seeds of Cannabis sativa L. were extracted under reflux with 60% EtOH-H2O, and the 60% EtOH-H2O elution fraction was identified as PHS with the UPLC-QTOF-MS. The 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice was used for behavioral and pharmacodynamic experiments. Behavioral symptoms were improved, Nissl-stained and TH-positive neurons in the substantia nigra were significantly increased in PHS-treated MPTP-induced PD model mice. Compared with the model group, PHS treatment reduced the expression level of α-syn, and the expression of TH increased significantly by western blotting, compared with the model group, the PHS group suppressed Caspase 3 and Bax expression and promoted Bcl-2 expression and levels of p62 decreased significantly, the ratio of LC3-II/I and p-mTOR/mTOR in the PHS group had a downward trend, suggesting that the therapeutic effect of PHS on MPTP-induced PD model mice may be triggered by the regulation of autophagy.

Comprehensive widely targeted metabolomics to decipher the molecular mechanisms of Dioscorea opposita thunb. cv. Tiegun quality formation during harvest.

Dioscorea opposita Thumb. cv. Tiegun is commonly consumed as both food and traditional Chinese medicine, which has a history of more than two thousand years. Harvest time directly affects its quality, but few studies have focused on metabolic changes during the harvesting process. Here, a comprehensive metabolomics approach was performed to determine the metabolic profiles during six harvest stages. Thirty eight metabolites with significant differences were determined as crucial participants. Related metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, stilbenoid, diarylheptanoid and gingerol biosynthesis, phenylpropanoid biosynthesis, flavonoid biosynthesis and tryptophan metabolism were the most active pathways during harvest. The results revealed that temperature has a significant impact on quality formation, which suggested that Dioscorea opposita thumb. cv. Tiegun harvested after frost had higher potential value of traditional Chinese medicine. This finding not only offered valuable guidance for yam production, but also provided essential information for assessing its quality.

Novel Multitarget ACE Inhibitory Peptides from Bovine Colostrum Immunoglobulin G: Cellular Transport, Efficacy in Regulating Endothelial Dysfunction, and Network Pharmacology Studies.

In this study, we used traditional laboratory methods, bioinformatics, and cellular models to screen novel ACE inhibitory (ACEI) peptides with strong ACEI activity, moderate absorption rates, and multiple targets from bovine colostrum immunoglobulin G (IgG). The purified fraction of the compound proteinase hydrolysate of IgG showed good ACEI activity. After nano-UPLC-MS/MS identification and in silico analysis, eight peptides were synthesized and verified. Among them, SFYPDY, TSFYPDY, FSWF, WYQQVPGSGL, and GVHTFP were identified as ACEI peptides, as they exhibited strong ACEI activity (with IC50 values of 104.7, 80.0, 121.2, 39.8, and 86.3 µM, respectively). They displayed good stability in an in vitro simulated gastrointestinal digestion assay. In a Caco-2 monolayer model, SFYPDY, FSWF, and WYQQVPGSGL exhibited better absorption rates and lower IC50 values than the other peptides and were thereby identified as novel ACEI peptides. Subsequently, in a H2O2-induced endothelial dysfunction (ED) model based on HUVECs, SFYPDY, FSWF, and WYQQVPGSGL regulated ED by reducing apoptosis and ROS accumulation while upregulating NOS3 mRNA expression. Network pharmacology analysis and RT-qPCR confirmed that they regulated multiple targets. Overall, our results suggest that SFYPDY, FSWF, and WYQQVPGSGL can serve as novel multitarget ACEI peptides.

Artemisinin reduces PTSD-like symptoms, improves synaptic plasticity, and inhibits apoptosis in rats subjected to single prolonged stress.

Post-Traumatic Stress Disorder (PTSD) is a chronic mental disorder characterized by symptoms of panic and anxiety, depression, impaired cognitive functioning, and difficulty in social interactions. While the effect of the traditional Chinese medicine artemisinin (AR) on PTSD is unknown, its therapeutic benefits have been demonstrated by studies on models of multiple neurological disorders. This study aimed to extend such findings by investigating the effects of AR administration on a rat model of PTSD induced by a regimen of single prolonged stress (SPS). After rats were subjected to the SPS protocol, AR was administered and its impact on PTSD-like behaviors was evaluated. In the present study, rats were subjected to a multitude of behavioral tests to evaluate behaviors related to anxiety, memory function, and social interactions. The expression of hippocampal synaptic plasticity-related proteins was detected using Western blot and immunofluorescence. The ultrastructure of synapses was observed under transmission electron microscopy. The apoptosis of hippocampal neurons was examined with Western blot, TUNEL staining, and HE staining. The results showed that AR administration alleviated the PTSD-like phenotypes in SPS rats, including behavior indicative of anxiety, cognitive deficits, and diminished sociability. AR administration was further observed to improve synaptic plasticity and inhibit neuronal apoptosis in SPS rats. These findings suggest that administering AR after the onset of severe traumatic events may alleviate anxiety, cognitive deficits, and impaired social interaction, improve synaptic plasticity, and diminish neuronal apoptosis. Hence, the present study provides evidence for AR's potential as a multi-target agent in the treatment of PTSD.

Core outcome sets for myocardial infarction in clinical trials of traditional Chinese medicine and Western medicine.

BACKGROUND: Clinical trials of traditional Chinese medicine (TCM) and Western medicine showed there was heterogeneity of outcome reporting in myocardial infarction (MI). Developing a core outcome set (COS) might improve the consistency of outcome reporting in future clinical trials. METHODS: A list of outcomes was developed based on a systematic review of randomized controlled trials (RCTs) of MI and semistructured interviews with MI patients. Two rounds of Delphi survey for clinicians, researchers, journal editors, and methodologists were conducted. An online questionnaire sent to nurses. After an online consensus meeting, a COS for MI RCTs was developed. RESULTS: After extracted data from clinical trials and discussed, 216 outcomes were included in round 1 of the Delphi survey. Seventy-four participants completed round 1 of the Delphi survey. Sixty-five participants completed round 2 of the Delphi survey. Twenty-two nurses completed the online questionnaire. Fifteen participants attended the online consensus meeting, and 14 of them voted and determined the final COS. For all types of MI, it was recommended that left ventricular ejection fraction and quality of life be measured and reported. For acute MI, the participants in the consensus meeting recommended the following core outcomes: death from cardio-cerebrovascular disease, cardiogenic shock, heart failure, troponin I, troponin T, creatine kinase isoenzyme, Killip class, target vessel revascularization, and emergency CABG. For previous MI, recurrent MI, recurrent angina pectoris, and heart failure readmission were recommended. CONCLUSIONS: The COS for MI in RCTs provides recommendations for clinical trials that seek to improve outcomes for patients with MI.

Structure and properties of acidic polysaccharides isolated from Massa Medicata Fermentata: Neuroprotective and antioxidant activity.

Massa Medicata Fermentata (MMF) is a fermented food with therapeutic effects. Previous studies suggested that after stir-frying, the uronic acid content in MMF crude polysaccharides increases, and the pH value decreases, which is caused by the change in acidic polysaccharides. However, the detailed physicochemical properties and structure-activity correlation of the acidic polysaccharides in MMF have not been fully explored. In this study, two acidic polysaccharides (SMMFAP and CMMFAP) were isolated from the MMF and its stir-fried product, respectively. Their structural characteristics and bioactivities were comparatively studied, and the structure-activity correlation was examined. Our findings revealed that the SMMFAP had a higher average Mw and higher Gal and Man content than the CMMFAP. Both the SMMFAP and CMMFAP were mainly composed of Xyl, Man, and Gal residues, whereas the CMMFAP had fewer linkage types. Additionally, the CMMFAP exhibited stronger neuroprotective activity than the SMMFAP owing to its higher content of 1,6-linked-Galp, while the SMMFAP exhibited better antioxidant activity, which might be related to its higher average Mw. Our findings suggest that acidic polysaccharides may be the active substances that cause differences in effectiveness between the sheng and chao MMF. Furthermore, the research qualified the SMMFAP and CMMFAP with different potential applications.

Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.

Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage. Hence, this study aimed to elucidate the association between mitophagy and skeletal fluorosis and the precise mechanisms through which calcium alleviates these injuries. A 100 mg/L sodium fluoride (NaF) exposure model in Parkin knockout (Parkin-/-) mice and a 100 mg/L NaF exposure mouse model with 1% calcium carbonate (CaCO3) intervention were established in the current study. Fluoride exposure caused the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy and mitochondrial apoptosis in the bones, which were restored after blocking Parkin. Additionally, the intervention model showed fluoride-exposed mice exhibited abnormal bone trabecula and mechanical properties. Still, these bone injuries could be effectively attenuated by adding 1% calcium to their diet, which reversed fluoride-activated mitophagy and apoptosis. To summarize, fluoride can activate bone mitophagy through the PINK1/Parkin pathway and mitochondrial apoptosis. Parkin-/- and 1% calcium provide protection against fluoride-induced bone damage. Notably, this study provides theoretical bases for the prevention and therapy of animal and human health and safety caused by environmental fluoride contamination.

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

INTRODUCTION: Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that ß-hydroxy ß-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. METHODS AND ANALYSIS: In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. ETHICS AND DISSEMINATION: This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences. TRIAL REGISTRATION NUMBER: NCT05525039.

Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Five new biflavonoids with acetylcholinesterase inhibitory activity from Diphylleia sinensis.

Five new biflavonoids, diphybiflavonoids A - E (1-5), were isolated from the roots and rhizomes of Diphylleia sinensis. Their structures were elucidated by extensive spectroscopic data, including UV, IR, HR-ESI-MS and 2D NMR. Their absolute configurations were determined by ECD spectra. All isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activity. Compounds 1-4 exhibited the potent AChE inhibitory activities with IC50 values of 1.62, 2.10, 2.08, and 5.15 µM, respectively. The preliminary structure-activity relationship study indicated that the connection mode (C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''') of biflavonoid subunits, and 3-hydroxy group of flavonol subunit were important structural factors for AChE inhibitory activity. Biflavonoids, containing a C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''' linkage, can be a potentially useful platform for development of cholinesterase inhibitors.

Bioinformatics-driven discovery of silica nanoparticles induces apoptosis and renal damage via the unfolded protein response in NRK-52E cells and rat kidney.

Silica nanoparticles (SiNPs) are nanomaterials with widespread applications in drug delivery and disease diagnosis. Despite their utility, SiNPs can cause chronic kidney disease, hindering their clinical translation. The molecular mechanisms underlying SiNP-induced renal toxicity are complex and require further investigation. To address this challenge, we employed bioinformatics tools to predict the potential mechanisms underlying renal damage caused by SiNPs. We identified 1627 upregulated differentially expressed genes (DEGs) and 1334 downregulated DEGs. Functional enrichment analysis and protein-protein interaction network revealed that SiNP-induced renal damage is associated with apoptosis. Subsequently, we verified that SiNPs induced apoptosis in an in vitro model of NRK-52E cells via the unfolded protein response (UPR) in a dose-dependent manner. Furthermore, in an in vivo rat model, high-dose SiNP administration via tracheal drip caused hyalinization of the renal tubules, renal interstitial lymphocytic infiltration, and collagen fiber accumulation. Concurrently, we observed an increase in UPR-related protein levels at the onset of renal damage. Thus, our study confirmed that SiNPs induce apoptosis and renal damage through the UPR, adding to the theoretical understanding of SiNP-related kidney damage and offering a potential target for preventing and treating kidney injuries in SiNP clinical applications.

Photobiomodulation therapy alleviates repeated closed head injury-induced anxiety-like behaviors.

Repeated closed head injury (rCHI) is one of the most common brain injuries. Although extensive studies have focused on how to treat rCHI-induced brain injury and reduce the possibility of developing memory deficits, the prevention of rCHI-induced anxiety has received little research attention. The current study was designed to assess the effects of photobiomodulation (PBM) therapy in preventing anxiety following rCHI. The rCHI disease model was constructed by administering three repeated closed-head injuries within an interval 5 days. 2-min daily PBM therapy using an 808 nm continuous wave laser at 350 mW/cm2 on the scalp was implemented for 20 days. We found that PBM significantly ameliorated rCHII-induced anxiety-like behaviors, neuronal apoptosis, neuronal injury, promotes astrocyte/microglial polarization to anti-inflammatory phenotype, preserves mitochondrial fusion-related protein MFN2, attenuates the elevated mitochondrial fission-related protein DRP1, and mitigates neuronal senescence. We concluded that PBM therapy possesses great potential in preventing anxiety following rCHI.

Effects of enzymolysis and fermentation of Chinese herbal medicines on serum component, egg production, and hormone receptor expression in laying hens.

OBJECTIVE: In the present study, we aimed to investigate the effects of enzymolysis fermentation of Chinese herbal medicines (CHMs) on egg production performance, egg quality, lipid metabolism, serum reproductive hormone levels, and the mRNA expression of the ovarian hormone receptor of laying hens in the late-laying stage. METHODS: A total of 360 Hy-Line Brown laying hens (age, 390 days) were randomly categorized into four groups. Hens in the control (C) group were fed a basic diet devoid of CHMs, the crushed CHM (CT), fermented CHM (FC), and enzymatically fermented CHM (EFT) groups received diets containing 2% crushed CHM, 2% fermented CHM, and 2% enzymatically fermented CHM, respectively. RESULTS: Compared with crushed CHM, the acid detergent fiber, total flavonoids, and total saponins contents of fermented CHM showed improvement (p<0.05); furthermore, the neutral and acid detergent fiber, total flavonoids, and total saponins contents of enzymatically fermented CHM improved (p<0.05). At 5 to 8 weeks, hens in the FC and EFT groups showed increased laying rates, haugh unit, albumin height, yolk color, shell thickness, and shell strength compared with those in the C group (p<0.05). Compared with the FC group, the laying rate, albumin height, and Shell thickness in the EFT group was increased (p<0.05). Compared with the C, CT, and FC groups, the EFT group showed reduced serum total cholesterol and increased serum luteinizing hormone levels and mRNA expressions of follicle stimulating hormone receptor and luteinizing hormone receptor (p<0.05). CONCLUSION: These results indicated that the ETF group improved the laying rate and egg quality and regulated the lipid metabolism in aged hens. The mechanism underlying this effect was likely related to cell wall degradation of CHM and increased serum levels of luteinizing hormone and mRNA expression of the ovarian hormone receptor.