Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

Effects of oral calcium on reproduction and postpartum health in cattle: a meta-analysis and quality assessment.

Postpartum blood calcium (Ca) concentration is related to the reproduction and health of cattle. Oral calcium supplements were given to dairy cows after calving to increase blood Ca concentration and reduce the risk of hypocalcemia. However, studies have shown that oral Ca has different effects in preventing disease. The purposes of this study were (i) to conduct a meta-analysis to evaluate the expected effect of oral Ca on incidence of calving-related diseases, pregnancy risk and milk yield in dairy cows, and (ii) to make a quality assessment of these related studies. In total, 22 eligible studies were included in this review. Meta-analysis showed that oral Ca could significantly reduce the incidence of hypocalcemia (clinical hypocalcemia: relative risk (RR) = 0.67, 95% confidence interval (CI) = [0.52, 0.87]; subclinical hypocalcemia: RR = 0.81, CI = [0.72, 0.91]), and incidence of retained placenta (RR = 0.77, CI = [0.62, 0.95]), improved blood Ca concentrations: mean difference (MD) = 0.08; 95% CI = [0.04, 0.11]. For other results, the meta-analysis revealed a lack of evidence of the correlation between oral Ca and serum magnesium (Mg) / phosphorus (P) concentration (Mg: MD = -0.04; 95% CI = [-0.10, 0.02]; P: MD = 0.05; 95% CI = [-0.10, 0.21]) or incidence of other calving-related disorders (metritis: RR = 1.06, CI = [0.94, 1.19]; ketosis: RR = 1.04, CI = [0.91, 1.18]; mastitis: RR = 1.02, CI = [0.86, 1.21]; displacement of the abomasum: RR = 0.81, CI = [0.57, 1.16]) or pregnancy risk (pregnancy risk at first service: RR = 0.99, CI = [0.94, 1.05]; overall pregnancy rate: RR = 1.03, CI = [0.98, 1.08]) or milk yield (MD = 0.44; 95% CI = [-0.24, 1.13]). The distribution of the funnel plot formed by the included studies was symmetrical, and the Egger's test had a p > 0.05, indicating that there was no significant publication bias. Sensitivity analyses results suggested that the results of meta-analysis are robust. Quality assessment of the included studies revealed that the risk of bias was focused on selection bias, performance bias, detection bias and other sources of bias, and the future research should focus on these aspects.

Protective effect of quercetin on lipopolysaccharide­induced miscarriage based on animal experiments and network pharmacology.

Spontaneous abortion (SA) occurs in woman of child­bearing age, jeopardizing their physical and mental health. Quercetin is a natural flavonoid, which exhibits a variety of pharmacological activities. However, the role and mechanisms of quercetin in SA still need to be further explored. Animal experiments were performed to examine the effect of quercetin in treating SA. Institute of Cancer Research mice were injected with lipopolysaccharide into the tail vein on the 7th day of gestation to establish a SA model. Gavage was performed during days 3­8 of gestation with high­, medium­ and low­dose of quercetin. Then the effect of quercetin on embryos was evaluated. Animal experiment showed that quercetin could remarkably reduce the embryo loss rate and increase the mean weight of surviving embryos to some degree. Furthermore, network pharmacology was employed to explore the underlying mechanisms of quercetin in the treatment of SA. Several databases were used to collect the targets of SA and quercetin. Protein­protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to elucidate the interactions between SA and quercetin. The relative mRNA expressions of several targets in uterine were detected by quantitative reverse transcriptase polymerase chain reaction (RT­qPCR). Network pharmacology indicated that the effects of quercetin in treating SA were mainly related to hormone response and the modulation of defense response and inflammatory response, involving signaling pathways such as PI3K­Akt, VEGF, MAPK and core targets such as AKT1, albumin, caspase­3. RT­qPCR showed that quercetin could up­regulate AKT1, MAPK1, PGR, SGK1 and down­regulate ESR1, MAPK3. The results showed that quercetin may modulate multiple signaling pathways by targeting core targets to prevent and treat SA.

Bioactive triterpenoid compounds of Poria cocos (Schw.) Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

Assessing the journey of calcium supplementation: A mendelian randomization study on the causal link between calcium levels and sleep disorders.

BACKGROUND & AIM: Sleep disorder is a growing concern, and calcium supplementation is often recommended as a potential intervention for sleep disorders. However, the causal relationship between calcium levels and the incidence of sleep disorders remains unclear. Mendelian randomization techniques utilizing genetic variants that affect calcium levels, can provide valuable insights into causality. This study aims to examine the association between calcium levels and sleep disorders in a diverse population that includes both adolescents and adults, and investigate the effects of calcium levels on sleep disorders. METHODS: Mendelian randomization analysis was conducted using data from UK Biobank and FinnGen datasets. The inverse-variance weighting (IVW) was selected as the primary method. In addition, traditional mediation analysis was performed on a subset of the NHANES data spanning from 2007 to 2018. RESULTS: Our findings provide evidence supporting a causal relationship between calcium intake and reduced risk of sleep disorders (beta = -0.079, SE = 0.0395, P = 0.0457). While not reaching statistical significance, other MR methods such as weighted median and Mr-Egger exhibited similar directional trends. Analysis of the NHANES cohort revealed a negative association between calcium levels and the prevalence of sleep disorders in male, black, and physically active populations. However, this association was not observed in other demographic groups. CONCLUSION: Our results suggested that there is no significant correlation between calcium levels and sleep disorder in non-exercise populations. This raises concerns about the long-term high-dose calcium supplementation in clinical practice, which requires further investigation.

Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients: a single-centre study.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.

Shh-Gli2-Runx2 inhibits vascular calcification.

BACKGROUND: In patients with chronic kidney disease (CKD), vascular calcification (VC) is common and is associated with a higher risk of all-cause mortality. Shh, one ligand for Hedgehog (Hh) signaling, participates in osteogenesis and several cardiovascular diseases. However, it remains unclear whether Shh is implicated in the development of VC. METHODS: Inorganic phosphorus 2.6 mM was used to induce vascular smooth muscle cells (VSMCs) calcification. Mice were fed with adenine diet supplement with 1.2% phosphorus to induce VC. RESULTS: Shh was decreased in VSMCs exposed to inorganic phosphorus, calcified arteries in mice fed with an adenine diet, as well as radial arteries from patients with CKD presenting VC. Overexpression of Shh inhibited VSMCs ostosteoblastic differentiation and calcification, whereas its silencing accelerated these processes. Likewise, mice treated with smoothened agonist (SAG; Hh signaling agonist) showed alleviated VC, and mice treated with cyclopamine (CPN; Hh signaling antagonist) exhibited severe VC. Additionally, overexpression of Gli2 significantly reversed the pro-calcification effect of Shh silencing on VSMCs, suggesting that Shh inhibited VC via Gli2. Mechanistically, Gli2 interacted with Runx2 and promoted its ubiquitin proteasomal degradation, therefore protecting against VC. Of interest, the pro-degradation effect of Gli2 on Runx2 was independent of Smurf1 and Cullin4B. CONCLUSIONS: Our study provided deeper insight to the pathogenesis of VC, and Shh might be a novel potential target for VC treatment.

Vitamin D3 supplementation shapes the composition of gut microbiota and improves some obesity parameters induced by high-fat diet in mice.

PURPOSE: Individuals with vitamin D (VD) insufficiency have a greater tendency to develop obesity and have increased systemic inflammation. Gut microbiota are involved in the regulation of host inflammation and energy metabolism, which plays a role in the pathogenesis of obesity. Thus, we aimed to evaluate the effects of different doses of VD3 on body weight, serum lipids, inflammatory factors, and intestinal barrier function in obese mice and to explore the regulatory effect of VD3 on gut microbiota in obese mice. METHODS: Male C57BL/6 J mice received a normal chow diet (NCD, 10% fat) or high-fat diet (HFD, 60% fat) to induce obesity within 10 weeks. Then, HFD mice were supplemented with 5650, 8475, or 11,300 IU VD3/kg diet for 8 weeks. Finally, 16 s rRNA analysis was performed to analyze gut microbiota composition in cecal contents. In addition, body weight, serum lipids, inflammatory factors, and intestinal barrier function were analyzed. RESULTS: VD3 supplementation reduced body weight and the levels of TG, TC, HDL-C, TNF-α, IL-1ß and LPS, and increased ZO-1 in HFD-fed mice. Moreover, it increased α-diversity, reduced F/B ratio and altered microbiota composition by increasing relative abundance of Bacteroidetes, Proteobacteria, Desulfovibrio, Dehalobacterium, Odoribacter, and Parabacteroides and reducing relative abundance of Firmicutes and Ruminococcus. There were significant differences between HFD and NCD groups in several metabolic pathways, including endotoxin biosynthesis, tricarboxylic acid cycle, lipid synthesis and metabolism, and glycolysis. CONCLUSIONS: Low, medium, and high doses of VD3 inhibited weight gain, reduced levels of blood lipids and inflammatory factors, and improved endotoxemia and gut barrier function in obese mice. It also increased the α-diversity of gut microbiota in obese mice and reduced the relative abundance of some intestinal pathogenic bacteria, increased the relative abundance of some beneficial bacteria, and corrected the intestinal flora disorder of obese mice, with the low- and high-dose groups showing better effects than the medium-dose group.

Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study).

Background: The efficacy of current adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. ctDNA could serve as a potential marker to identify patients who are at higher risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly improve clinical outcome, albeit such evidence is rare in GA/GEJA. Here, we intend to explore the clinical benefit of the reinforcement of adjuvant immunotherapy and antiangiogenics alongside with chemotherapy in patients who are deemed in high risk of recurrence by ctDNA analysis, which might shed light on further improvements in adjuvant therapy for GA/GEJA. Methods/Design: This study is designed as a prospective, multicenter, randomized, controlled phase II study in patients histologically or cytologically diagnosed with GA/GEJA who underwent D2 gastrectomy and achieved R0 or R1 resection. From February 2022, a total of 300 stage III patients will be enrolled and subjected according to ctDNA sequencing results, and those with positive results will subsequently be randomized 1:1 to arm A or B. Patients in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while patients in arm B will receive XELOX alone for 6-8 cycles. ctDNA-negative patients will be assigned to arm C, and patients who are ctDNA positive but failed in randomization will be assigned to arm D. Patients in arms C and D will receive the investigator's choice of therapy. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the DFS of ctDNA positive patients versus ctDNA negative patients, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules on the treatment response, adverse events (AEs), and the impact of nutrition status or exercise on recurrence. Discussion: We expect that ctDNA would be a strong prognostic factor and ctDNA-positive patients are at higher risk of relapse than ctDNA-negative patients. The addition of anlotinib and penpulimab to XELOX, may contribute to delaying relapse in ctDNA-positive patients. Trial registration: https://www.clinicaltrials.gov, identifier NCT05494060.

Optimization of trans-4-hydroxyproline synthesis pathway by rearrangement center carbon metabolism in Escherichia coli.

BACKGROUND: trans-4-Hydroxyproline (T-4-HYP) is a promising intermediate in the synthesis of antibiotic drugs. However, its industrial production remains challenging due to the low production efficiency of T-4-HYP. This study focused on designing the key nodes of anabolic pathway to enhance carbon flux and minimize carbon loss, thereby maximizing the production potential of microbial cell factories. RESULTS: First, a basic strain, HYP-1, was developed by releasing feedback inhibitors and expressing heterologous genes for the production of trans-4-hydroxyproline. Subsequently, the biosynthetic pathway was strengthened while branching pathways were disrupted, resulting in increased metabolic flow of α-ketoglutarate in the Tricarboxylic acid cycle. The introduction of the NOG (non-oxidative glycolysis) pathway rearranged the central carbon metabolism, redirecting glucose towards acetyl-CoA. Furthermore, the supply of NADPH was enhanced to improve the acid production capacity of the strain. Finally, the fermentation process of T-4-HYP was optimized using a continuous feeding method. The rate of sugar supplementation controlled the dissolved oxygen concentrations during fermentation, and Fe2+ was continuously fed to supplement the reduced iron for hydroxylation. These modifications ensured an effective supply of proline hydroxylase cofactors (O2 and Fe2+), enabling efficient production of T-4-HYP in the microbial cell factory system. The strain HYP-10 produced 89.4 g/L of T-4-HYP in a 5 L fermenter, with a total yield of 0.34 g/g, the highest values reported by microbial fermentation, the yield increased by 63.1% compared with the highest existing reported yield. CONCLUSION: This study presents a strategy for establishing a microbial cell factory capable of producing T-4-HYP at high levels, making it suitable for large-scale industrial production. Additionally, this study provides valuable insights into regulating synthesis of other compounds with α-ketoglutaric acid as precursor.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

Effect of vitamin D3 on lipid droplet growth in adipocytes of mice with HFD-induced obesity.

Vitamin D-regulating action of PPARγ on obesity has been confirmed on adipocyte differentiation. However, it is not clear whether vitamin D affects the morphological size of mature adipocytes by influencing the expression of PPARγ in vivo. Our hypothesis was that Vitamin D3 (VitD3) inhibits the growth of adipocyte size by suppressing PPARγ expression in white adipocytes of obese mice. Five-week-old male C57BL/6J mice were randomly divided into normal diet and high-fat diet groups. After 10 weeks, the body weight between the two groups differed by 26.91%. The obese mice were randomly divided into a high-fat diet, solvent control, low-dose VitD3 (5000 IU/kg·food), medium-dose VitD3 (7500 IU/kg·food), high-dose VitD3 (10,000 IU/kg·food), and PPAR γ antagonist group, and the intervention lasted for 8 weeks. Diet-induced obesity (DIO) mice fed high-dose VitD3 exacerbated markers of adiposity (body weight, fat mass, fat mass rate, size of white and brown adipocytes, mRNA, and protein levels of ATGL and Fsp27), and the protein level of ATGL and Fsp27 decreased in the low-dose group. In conclusion, high-dose VitD3 possibly via inhibiting the ATGL expression, thereby inhibiting lipolysis, increasing the volume of adipocytes, and decreasing their fat-storing ability resulted in decreased Fsp27 expression. Therefore, long-term high-dose oral VitD3 may not necessarily improve obesity, and we need more clinical trials to explore the intervention dose and duration of VitD3 in the treatment of VitD3 deficiency in obese patients.

Biofeedback physical regulation of hypertension based on acupoints: A clinical trial.

BACKGROUND: Hypertension is a predominant risk factor for cardiovascular disease and has imposed a global disease burden. Poor medication compliance is the major obstacle to antihypertensive drug therapy, and negative mood status is also detrimental to blood pressure (BP) management. While transcutaneous electrical acupoint stimulation (TEAS), as an electrical stimulation modality for biofeedback physical regulation based on acupoints, offers a such nondrug alternative option that is noninvasive, safe, and effective with high adherence. However, the optimal stimulation parameters of TEAS for hypertension remain unclear, especially the frequency, which needs further exploration. OBJECTIVE: The study aims to investigate the efficacy of TEAS for hypertension, and to screen the optimal electrical stimulation frequency. METHODS: This is an 8-week, randomized, controlled pilot trial with 3 parallel groups. In a ratio of 1:1:1, 120 patients with stage 1 hypertension will be divided into the TEAS-2Hz group, TEAS-10Hz group, or usual care group. All patients will receive the usual care for hypertension including lifestyle education, etc. Additionally, the 2 TEAS groups will receive 12 sessions of TEAS interventions at 2 Hz or 10 Hz, 3 times weekly for 30 minutes each, with 4 weeks of follow-up. The main outcome will be the change from baseline to week 4 in systolic BP among the groups. Secondary outcomes consist of changes in diastolic BP, mean arterial pressure, heart rate, heart rate variability, medication adherence, and quality of life. The safety outcomes will be any adverse event during the treatment. DISCUSSION: As a pre-study for the next large clinical trial of TEAS for hypertension, this study will offer references for optimized frequency of biofeedback electrical devices and promote more consciousness of the benefits of body-mind holistic regulation of BP, thereby achieving proactive and overall process management of BP.

The factors affecting neurogenesis after stroke and the role of acupuncture.

Stroke induces a state of neuroplasticity in the central nervous system, which can lead to neurogenesis phenomena such as axonal growth and synapse formation, thus affecting stroke outcomes. The brain has a limited ability to repair ischemic damage and requires a favorable microenvironment. Acupuncture is considered a feasible and effective neural regulation strategy to improve functional recovery following stroke via the benign modulation of neuroplasticity. Therefore, we summarized the current research progress on the key factors and signaling pathways affecting neurogenesis, and we also briefly reviewed the research progress of acupuncture to improve functional recovery after stroke by promoting neurogenesis. This study aims to provide new therapeutic perspectives and strategies for the recovery of motor function after stroke based on neurogenesis.

Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis.

This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I2 = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I2 = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I2 = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I2 = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I2 = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENTWhat is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women.What do the results of this study add? This systematic review and meta-analysis of data from ten studies (n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls.What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.

Micellar nanoparticles inhibit breast cancer and pulmonary metastasis by modulating the recruitment and depletion of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are notorious for their pathological characteristics of immunosuppression and their promoting effect on cancers. They can induce the formation of pre-metastatic niche (PMN) characterized by inflammation, immunosuppression and vascular leakage, and promote pulmonary metastasis of breast cancer. Herein, a tumor targeting c(RGDfk) peptide modified low molecular-weight-heparin-all-trans-retinoic-acid (LMWH-ATRA) micellar nanoparticle loaded with chemotherapeutic drug doxorubicin (DOX) and immune adjuvant α-galactosylceramide (αGC) (RLA/DOX/αGC NP) was developed. The hydrophilic segment LMWH inhibited the recruitment of MDSCs by competitively binding with P-selectin on the surface of vascular endothelial cells (VECs), while the hydrophobic segment ATRA promoted the depletion of MDSCs by inducing their differentiation. Through the modulation of MDSCs, micelles can significantly improve the inflammatory and immunosuppressive microenvironment of the lung and tumor sites, and inhibit the formation of PMN. Not only this, the micelles also produced a synergistic effect with αGC, which effectively improved the anti-tumor immunity of tumor bearing mice and provided a promising therapeutic strategy for breast cancer and pulmonary metastasis.

Camellia Seed Cake Extract Supports Hair Growth by Abrogating the Effect of Dihydrotestosterone in Cultured Human Dermal Papilla Cells.

Autocrine and paracrine factors play key roles in the process of Androgenetic alopecia (AGA), which are secreted by balding dermal papilla cells (DPCs) after dihydrotestosterone (DHT) induction. Camellia seed cake is an oriental oil extraction byproduct, and its extract has been traditionally used to wash hair in China. This study elucidated the hair growth-promoting effects of Camellia seed cake extract (CSCE) in DHT-treated cultured DPCs and its underlying mechanisms. The effect of CSCE on cell viability and release of inflammatory factors IL-6 and IL-1α was performed on human dermal papilla cells (DPCs) incubated with DHT. Relative expression of bax, bcl-2, p53, androgen receptor (AR) and 5α- reductase type II (SRD5A2) was determined by PCR. Senescence-associated was examined by ß-galactosidase (SA-ß-Gal) assays. CSCE restored DHT-induced cell damage in a dose-dependent manner, and effectively reduced the production of IL-6 and IL-1α in DHT-treated DPCs. CSCE exhibited an anti-apoptotic effect, which increased the expression of bcl-2, and decreased the expressions of bax and p53 in DHT-incubated DPCs. CSCE also showed an anti-androgenic effect reversing the increase in AR and SRD5A2 expressions in DPCs driven by DHT incubation. In addition, CSCE inhibited the ß-galactosidase enzyme activity and slowed down the cell senescence of DPCs which is crucial for AGA progression. In this study, we found that CSCE may have the potential to prevent and alleviate AGA by abrogating the effect of DHT in cultured DPCs.

Effect of Light Treatment on Chemical Composition of Andrographis paniculata Seedlings.

Light quality consists of a spectrum of different bands, which not only affects plant, development, and primary metabolism but also affects the secondary metabolism of plants. It is an important factor affecting the content of active components of medicinal plants. The A. paniculata seedlings planted in the laboratory, as materials, were tested with red light, far red light, blue light, and ultraviolet light separately. The study assays the content of six main chemical components separately by LC-MS, observes the changes in the content, and analyzes the relationship between the light quality and the active ingredient of A. paniculata. Using the ointment yield and pH value, the fingerprint analysis method of A. paniculata standard decoction was established, and we discussed the selection of index components of A. paniculata standard decoction. It was suggested to select andrographolide as the index component. It will provide a theoretical basis for the large area cultivation of A. paniculata and optimize the quality of medicinal materials to ensure the quality of standard decoction.

Hair growth-promoting effects of Camellia seed cake extract in human dermal papilla cells and C57BL/6 mice.

OBJECTIVES: Camellia seed cake is a by-product of Camellia oleifera Abel seed after oil extraction. Washing hair with Camellia seed cake extract is a traditional Chinese custom that has lasted for over one thousand years. However, the hair growth-promoting effects of Camellia seed cake extract were not investigated so far. This work examined the effects of de-saponinated Camellia seed cake extracts (DS-CSE) on hair growth, using in vitro and in vivo models. METHODS: The studies on cell proliferation, cell cycle regulation, and K+ channels activation effects of DS-CSE were performed on human dermal papilla cells (DPCs). Relative expression of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and transforming growth factor-ß (TGF-ß1) in DPCs was determined by RT-PCR. Relative expression of ERK and AKT was determined by Western blot analysis. Hair growth-promoting effects were also measured in C57BL/6J mice model. RESULTS: DS-CSE treatment significantly proliferated DPCs, relating to the increased proportion of DPCs in S and G2 /M phases, the activation of potassium channels and the promoted phosphorylation of ERK and AKT in DPCs. DS-CSE treatment also significantly upregulated the mRNA levels of HGF, VEGF and IGF-1, and downregulated the mRNA level of TGF-ß1. Topical application of DS-CSE promoted hair growth on shaven back mice and also upregulated the expression of VEGF in mice. CONCLUSION: Our results demonstrated that DS-CSE exerts a hair growth-promoting effect in vitro and in vivo by proliferating DPCs through the ERK and AKT signaling pathways and regulating the expression of growth factors.

Isorhamnetin alleviates lipopolysaccharide-induced acute lung injury by inhibiting mTOR signaling pathway.

Aim: Acute Lung Injury (ALI) is an acute hypoxic respiratory insufficiency caused by various traumatic factors, manifested as progressive hypoxemia and respiratory distress, and lung imaging shows a heterogeneous osmotic outbreak. Isorhamnetin (ISO) is a flavonoid compound isolated and purified from medicinal plants, such as Hippophae rhamnoides L. and Ginkgo, and has multiple pharmacological functions, such as anti-tumor, anti-myocardial hypoxia, and cardiovascular protection. Our previous study has shown that ISO could attenuate lipopolysaccharide (LPS)-induced acute lung injury in mice, but its mechanism is not clear.Methods: In this study, we used LPS-induced mouse and cell models to research the mechanism of ISO alleviating acute lung injury.Results: The results showed that ISO could attenuate the injury of type II alveolar epithelial cells by inhibiting the TLR4/NF-κB pathway. Further studies showed that ISO could inhibit the activation of mTOR signal in vivo and in vitro and promote autophagy in alveolar epithelial cells to reduce lung injury caused by LPS. In addition, ISO could inhibit LPS-induced epithelial cell apoptosis.Conclusion: Overall, ISO could suppress injury and apoptosis of epithelial cells and activate autophagy to protect epithelial cells via inhibiting mTOR signal and attenuating LPS-induced acute lung injury in mice.