Efficacy of Sailuotong on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer's disease.

OBJECTIVE: To discuss the influence of Sailuotong (, SLT) on the Neurovascular Unit (NVUs) of amyloid precursor protein (APP)/presenilin-1(PS1) mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease (AD). METHODS: The mice were allocated into the following nine groups: (a) the C57 Black (C57BL) sham-operated group (control group), (b) ischaemic treatment in C57BL mice (the C57 ischaemic group), (c) the APP/PS1 sham surgery group (APP/PS1 model group), (d) ischaemic treatment in APP/PS1 mice (APP/PS1 ischaemic group), (e) C57BL mice treated with aspirin following ischaemic treatment (C57BL ischaemic + aspirin group), (f) C57BL mice treated with SLT following ischaemic treatment (C57BL ischaemic + SLT group), (g) APP/PS1 mice treated with SLT (APP/PS1 + SLT group), (h) APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment (APP/PS1 ischaemic + donepezil hydrochloride group) and (i) APP/PS1 mice treated with SLT following ischaemic treatment (APP/PS1 ischaemic + SLT group). The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism. The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice. The hippocampus of each mouse was observed by haematoxylin and eosin (HE) and Congo red staining. The ultrastructure of NVUs in each group was observed by electron microscopy, and various biochemical indicators were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression level was detected by Western blot. The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice, which were restored by SLT. The results of HE staining showed that SLT restored the pathological changes of the NVUs. The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice. Furthermore, SLT significantly reduced the content of Aß, improved the vascular endothelium and repaired the mitochondrial structures. The ELISA detection, western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor (VEGF), angiopoietin and basic fibroblast growth factor, as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1 (LRP-1) and VEGF in brain tissue. CONCLUSIONS: By increasing the expression of VEGF, SLT can promote vascular proliferation, up-regulate the expression of LRP-1, promote the clearance of Aß and improve the cognitive impairment of APP/PS1 mice. These results confirm that SLT can improve AD by promoting vascular proliferation and Aß clearance to protect the function of NVUs.

Smart antimicrobial system based on enzyme-responsive high methoxyl pectin-whey protein isolate nanocomplex for fresh-cut apple preservation.

The increase in pectin methylesterase (PME) activity on fresh-cut apple surface can smartly trigger the controlled release of bactericidal agents encapsulated within intelligent responsive Pickering emulsions. In this study, we developed a PME-responsive nanocomplex (W-H-II) to stabilize Pickering emulsion containing thyme essential oil (TEO), preserving fresh-cut apples. W-H-II, formed by heat-induced whey protein isolate (WPI) and high methoxyl pectin (HMP) (pH 4.5, 85 °C, 15 min, WPI:HMP ratio 1:2), exhibited good pH stability due to the stabilizing effects of hydrophobic, hydrogen bonding, and electrostatic interactions. The presence of PME triggered the demethylation of HMP within W-H-II, conferring PME response characteristics. Subsequently, a bacteriostasis experiment with pectinase-producing Bacillus subtilis provided evidence of PME-triggered TEO release from W-H-II-stabilized Pickering emulsion. Furthermore, microscopy techniques were employed to verify the demulsification behavior of the emulsion when PME activity ranged from 0.25 to 2.50 U mL-1. Finally, the PME-responsive TEO Pickering emulsion effectively preserved fresh-cut apples. Stored for 6 days at 5 °C and 10 °C, as the PME activity on the apple surface increased, the decay rate of the coated group was 0 %, with a total colony count below 3.0 log CFU g-1. This study introduces a novel intelligent preservation strategy for storing fresh-cut apples.

Determinants affecting the blood mercury levels of preschool children in Shanghai, China: A cross-sectional study.

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.

Melatonin induces cell cycle arrest and suppresses tumor invasion in urinary bladder urothelial carcinoma.

Urinary bladder urothelial carcinoma (UBUC) encompasses about 90% of all bladder cancer cases, and the mainstream treatment is the transurethral resection of the bladder tumor followed by intravesical instillation. High rates of mortality, recurrence, and progression in bladder cancer have stimulated the search for alternative adjuvant therapies. The aim of this study was to investigate the potential of melatonin as adjuvant therapy in bladder cancer. Cell viability and clonogenic ability were assessed by an MTT assay and colony formation. Cell cycle and apoptosis analysis were performed by flow cytometry and Hoechst 33342 staining, while cell metastasis capacity was measured by wound healing and transwell assays. Potential mechanisms were investigated by an oncology array and verified via western blotting. The melatonin treatment significantly reduced T24 and UMUC3 bladder cancer cell proliferation and clonogenic ability. G1 arrest and sub-G1 accumulation in the T24 and UMUC3 cells led to cell proliferation suppression and cell death, and Hoechst 33342 staining further verified the apoptosis induction directly by melatonin. Moreover, melatonin weakened cell motility and invasiveness. Based on the oncology array results, we demonstrated that melatonin exerts its anti-cancer effect by down-regulating the HIF-1α and NF-κB pathways and downstream pathways, including Bcl-2, leading to cell cycle arrest and apoptosis induction in the UBUC cells. Overall, these findings support the potential of melatonin as adjuvant therapy in bladder cancer.

Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease.

Background: Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children. Methods: We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy. Results: Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029). Conclusion: This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.

Signaling pathways in Parkinson's disease: molecular mechanisms and therapeutic interventions.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and its treatment remains a big challenge. The pathogenesis of PD may be related to environmental and genetic factors, and exposure to toxins and gene mutations may be the beginning of brain lesions. The identified mechanisms of PD include α-synuclein aggregation, oxidative stress, ferroptosis, mitochondrial dysfunction, neuroinflammation, and gut dysbiosis. The interactions among these molecular mechanisms complicate the pathogenesis of PD and pose great challenges to drug development. At the same time, the diagnosis and detection of PD are also one of obstacles to the treatment of PD due to its long latency and complex mechanism. Most conventional therapeutic interventions for PD possess limited effects and have serious side effects, heightening the need to develop novel treatments for this disease. In this review, we systematically summarized the pathogenesis, especially the molecular mechanisms of PD, the classical research models, clinical diagnostic criteria, and the reported drug therapy strategies, as well as the newly reported drug candidates in clinical trials. We also shed light on the components derived from medicinal plants that are newly identified for their effects in PD treatment, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for PD therapy.

Electroacupuncture at Baliao points for erectile dysfunction after stroke: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of electroacupuncture at Baliao points in patients with erectile dysfunction after stroke.@*METHODS@#A total of 58 patients with erectile dysfunction after stroke were randomly divided into an observation group (29 cases, 1 case dropped off, 1 case discontinued) and a control group (29 cases, 1 case dropped off). Both groups were given basic treatment, including routine medical treatment, routine acupuncture treatment, rehabilitation training and pelvic floor biofeedback electrical stimulation treatment. The observation group was treated with electroacupuncture at Baliao points, and the control group was treated with shallow acupuncture combined with electroacupuncture at the control points (8 points at 20 mm horizontally beside Baliao points), continuous wave, frequency in 50 Hz, current intensity in 1-5 mA, 5 times a week for 4 weeks. The 5-item version of the international index of erectile function (IIEF-5) score, erectile dysfunction effect on quality of life (ED-EQoL) score and pelvic floor muscle contraction amplitude were compared between the two groups before and after treatment.@*RESULTS@#After treatment, the IIEF-5 scores and the contraction amplitude of fast muscle fiber, comprehensive muscle fiber and slow muscle fiber in the two groups were higher than those before treatment (P<0.05), the ED-EQoL scores were lower than those before treatment (P<0.05), and the changes of above indexes in the observation group were larger than the control group (P<0.05).@*CONCLUSION@#Electroacupuncture at Baliao points can improve the erectile function of patients with erectile dysfunction after stroke, increase the contraction amplitude of pelvic floor muscles, and promote the quality of life of patients.

Study on acupoint selection law of acupuncture for autism spectrum disorder based on data mining / 国际中医中药杂志

Objective:To analyze the acupoint selection law of acupuncture for autism spectrum disorder (ASD) using data mining techniques.Methods:Literature related to acupuncture for ASD was retrieved from the CNKI, SinoMed, VIP, Wanfang, and PubMed databases from the establishment of the databases to April 1, 2022, and then a database of acupuncture prescriptions was established. The frequency analysis of acupoint use was performed using Microsoft Excel 2019; the Apriori algorithm was used to analyze the association law of acupoints/acupoint areas; SPSS 26.0 was used to perform intergroup cluster analysis.Results:A total of 97 relevant articles with 97 acupuncture prescriptions and 98 acupoints/acupoint areas were included. The most frequently used acupoint was Shenmen (HT 7). The acupoint area of Jin's three-needle therapy and the Governor Vessel acupoints are commonly used. The most frequently occurring part of the acupoint/acupoint area was the head, and the most commonly used specific acupoint was the rendezvous acupoint. Association rule analysis yielded 40 groups of acupoints/acupoint areas, and the most commonly used combination was Laogong (PC 8) and Shenmen (HT 7). Four categories were extracted among high-frequency acupoints/acupoint areas by cluster analysis.Conclusion:Acupuncture treatment for ASD mainly selects the head acupoints, mainly selecting the acupoint area of Jin's three-needle therapy and the Governor Vessel acupoints, and paying attention to the use of specific acupoints.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Emerging pharmaceutical therapeutics and delivery technologies for osteoarthritis therapy.

Osteoarthritis (OA) is one of the most common joint degenerative diseases in the world. At present, the management of OA depends on the lifestyle modification and joint replacement surgery, with the lifespan of prosthesis quite limited yet. Effective drug treatment of OA is essential. However, the current drugs, such as the non-steroidal anti-inflammatory drugs and acetaminophen, as well as glucosamine, chondroitin sulfate, hyaluronic acid, are accompanied by obvious side effects, with the therapeutic efficacy to be enhanced. Recently, novel reagents such as IL-1 antagonists and nerve growth factor inhibitors have entered clinical trials. Moreover, increasing evidence demonstrated that active ingredients of natural plants have great potential for treating OA. Meanwhile, the use of novel drug delivery strategies may overcome the shortcomings of conventional preparations and enhance the bioavailability of drugs, as well as decrease the side effects significantly. This review therefore summarizes the pathological mechanisms, management strategies, and research progress in the drug molecules including the newly identified active ingredient derived from medicinal plants for OA therapy, with the drug delivery technologies also summarized, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for OA therapy.

Epidemiology of sepsis in Beijing from 2012 to 2018: analysis of hospital homepage databases derived from the Beijing Public Health System.

BACKGROUND: We aimed to evaluate the epidemiology of sepsis in secondary and tertiary hospitals in Beijing, China between 2012 and 2018 using information derived from the Beijing Public Health System. METHODS: The Beijing Public Health System accessed hospital homepage databases and identify patients who diagnosed sepsis or associated condition according to the International Classification of Diseases, 10th Edition, Clinical Modification codes. There are 125 hospitals involved in this study, including 61 secondary hospitals, accounting for 49.2%, and 63 tertiary hospitals, accounting for 50.8%. Patients were stratified by age as minors (0-17 years old), adults (18-64 years old), seniors (65-84 years old), and the elderly (≥ 85 years old). Patient's demographic information, treatments, outcomes, and all-cause hospitalization cost were evaluated. RESULTS: This study involved 8,597 patients. Patients treated in tertiary hospitals or received blood transfusion decreased with age, while patients who were male, received ventilation, or took Traditional Chinese Medicine, and in-hospital mortality and hospitalization cost, increased with age. There were 2,729 (31.7%) deaths in this study. A slight increase in in-hospital mortality occurred from 2012 to 2018. Median hospitalization cost for all patients was ¥29,453 (15,011, 65,237). Hospitalization cost showed no significant change from 2012 to 2016, but increased in 2017 and 2018. CONCLUSION: Sepsis is associated with high mortality and cost. From 2012 to 2018, in-hospital mortality and hospitalization cost of sepsis in Beijing increased significantly with age, and slightly by year.

Formation Mechanism of Microbial Diversity in Artificial Intelligence Devices due to Intermediate Disturbance by Low-Dose UV Radiation for Complementary Medicine.

The development of artificial intelligence devices in the complementary medicine field is rapid and the surface microbial diversity pollution was found with periodic low-dose ultraviolet radiation (LDUVR). Since artificial intelligence devices do not have enough different types of substrates for microbial communities, it is unclear how the great microbial diversity can emerge and persist, as this clearly defies the competitive exclusion principle of ecology. In this study, the 5 most common genera in the artificial intelligence devices, Escherichia, Pseudomonas, Streptococcus, Staphylococcus and Aeromonas have been sampled without and with periodic LDUVR, respectively. A new hypothesis was put up to clarify the construction and maintenance process of high microbiological diversity in artificial intelligence devices by comparing and evaluating the variations between the dynamic response characteristics of their relative abundances in the two scenarios as follows: the periodic LDUVR can be regarded as an adverse factor with intermediate disturbance, causing stronger microbial stochastic growth responses (SGR) which would inevitably give rise to stronger random variation of the other important processes tightly correlated with SGR, such as intra- and interspecific competition process, and substrates production and consumption process, which could effectively diminish the auto- and cross-correlation of stochastic processes of microbial populations, alleviating the intra- and inter-specific competitions. In artificial intelligence devices with LDUVR, these crucial succession processes can propel the microbial communities to generate and sustain a high species diversity. Finally, thorough Monte Carlo simulations were used to thoroughly confirm the idea. This research can build the theoretical groundwork, offer fresh viewpoints, and suggest potential microbial prevention strategies for the succession of microbial communities in LDUVR.

BMI, Blood Pressure, and Plasma Lipids among Centenarians and Their Offspring.

BACKGROUND: The burden of cardiovascular diseases (CVDs) is increasing substantially due to population growth and aging. Determining effective prevention and understanding the underlying mechanisms remain desirable pursuits for increasing the quality of life. As centenarians and their offspring may have genetic advantages, they may present with healthier cardiovascular-related profiles. METHODS: We launched a cross-sectional household-based survey of centenarian families, including 253 centenarians, 217 centenarian offspring, and 116 offspring spouses without centenarian parents from county-level Chinese longevity city Rugao. Among offspring and offspring spouses were the following arrangements: 101 paired offspring and offspring spouses who lived together, 116 unpaired offspring, and 16 unpaired spouses. We investigated their cardiovascular-related health status including waist circumference, body mass index (BMI), blood pressure, and plasma lipids and compared results among centenarians, centenarian offspring, and offspring spouses. RESULTS: Centenarians ranged from 99 to 109 years with a median age of 100 years. Centenarian offspring, with a median age of 70 years, and offspring spouses, with a median age of 69 years, shared similar age. Results of blood pressure, plasma lipid levels, and BMI displayed no significant difference between centenarian offspring and offspring spouses. However, centenarians appeared to have lower waist circumference, BMI, TC, LDL-C, TG, and diastolic blood pressure but higher levels of systolic blood pressure (p < 0.05). Multivariate analysis showed the prevalence of obesity, hypertension, and dyslipidemia was similar between centenarian offspring and offspring spouses, while centenarians appeared to have a lower prevalence of obesity and a higher prevalence of hypertension (p < 0.05). CONCLUSIONS: Centenarians and centenarian offspring did not present healthier BMI, blood pressure, or plasma lipids than offspring spouses. Further research on longevity and cardiovascular diseases are desirable.

A gradient-based discriminant analysis method for process quality control of carbonized TCM via Fourier transform near infrared spectroscopy: A case study on carbonized Typhae Pollen.

Carbonized traditional Chinese medicine (TCM) is a kind of distinctive traditional drug which has been widely used in various bleeding syndromes for over two thousand years, and most of them are still in clinical use. Although they share similar processing method: stir-frying, there are no specific quality standards and few quality control researches carried out on carbonized TCM up until now. Carbonized Typhae Pollen (CTP) is a typical carbonized TCM with efficacy of eliminating blood stasis and stanching bleeding. In this study, a novel process quality control model coupled with near infrared spectroscopy was established, called Gradient-based Discriminant Analysis method (GDA). Compared with conventional modeling methods (Convolutional Neural Network, Linear Discriminant Analysis, Standard Normal Variate-LDA), GDA model applied in fiber optic probe acquisition mode exhibited highest test accuracy (0.961), satisfactory correct identification (internal validation, 100%; external validation, 97.1%) and excellent model stability. This method provided a perfect guideline for process quality control of Carbonized TCM as well as ensured their clinical efficacy.

Extracts of Poria cocos polysaccharides improves alcoholic liver disease in mice via CYP2E1 and NF-κB inflammatory pathways / 中国中药杂志

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Anti-tumor Effect and Mechanisms of Triterpenoids and Polysaccharides in Ganoderma lucidum： A Review / 中国实验方剂学杂志

With the population aging， the morbidity and mortality of cancer patients continue to rise. At present， the treatment methods for tumors include surgery， chemotherapy， radiotherapy， targeted therapy， and immunotherapy. However， most chemotherapeutic drugs can cause severe side effects and drug resistance. Therefore， as an alternative therapy， traditional Chinese medicine （TCM） treatment can effectively relieve the clinical symptoms of tumor patients， improve the quality of life， inhibit or stabilize the development of tumors， and prolong the survival period of patients. Due to the good safety of Chinese medicine， its potential anti-cancer activity has attracted increasing attention. Ganoderma lucidum， a treasure of Chinese medicinal material， is a medicinal fungus with a history of more than 2 000 years in China. So far， many studies have proposed the anti-cancer properties of G. lucidum. G. lucidum has extensive pharmacological activities， such as anti-tumor， anti-atherosclerosis， and anti-aging. It can also regulate immunity， protect the liver and the heart， and reduce blood glucose and lipid. The chemical composition of G. lucidum is complex. At present， it is proved to contain polysaccharides， triterpenoids， alkaloids， nucleosides， amino acids， and various trace elements. The anti-tumor mechanisms of polysaccharides and triterpenoids in G. lucidum are mainly achieved by apoptosis induction， immune regulation， anti-angiogenesis， and induction of cell cycle arrest. Currently， it has been widely used in the adjuvant treatment of complex tumors such as lung cancer， liver cancer， cervical cancer， prostate cancer， breast cancer， and colon cancer. The present study reviewed the bioactivities and mechanisms of triterpenoids and polysaccharides in G. lucidum in recent years and highlighted the anti-tumor effects and mechanisms to provide references for the further development and utilization of G. lucidum.

Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis.

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in clinical models of osteoarthritis (OA). However, effects of MSC-derived exosomes on OA remain unclear. The study aimed to investigate the therapeutic potential of exosomes from human bone marrow MSCs (BM-MSCs) in alleviating OA. The anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery were performed on the knee joints of a rat OA model, followed by intra-articular injection of BM-MSCs or their exosomes. In addition, BM-MSC-derived exosomes were administrated to primary human chondrocytes to observe the functional and molecular alterations. Both of BM-MSCs and BM-MSC-derived exosomes alleviated cartilage destruction and subchondral bone remodelling in OA rat model. Administration of BM-MSCs and exosomes could reduce joint damage and restore the trabecular bone volume fraction, trabecular number and connectivity density of OA rats. In addition, in vitro assays showed that BM-MSCs-exosomes could maintain the chondrocyte phenotype by increasing collagen type II synthesis and inhibiting IL-1ß-induced senescence and apoptosis. Furthermore, exosomal lncRNA MEG-3 also reduced the senescence and apoptosis of chondrocytes induced by IL-1ß, indicating that lncRNA MEG-3 might partially account the anti-OA effects of BM-MSC exosomes. The exosomes from BM-MSCs exerted beneficial therapeutic effects on OA by reducing the senescence and apoptosis of chondrocytes, suggesting that MSC-derived exosomes might provide a candidate therapy for OA treatment.

The beneficial effects of ultraviolet light supplementation on bone density are associated with the intestinal flora in rats.

The general public spends one-third of its time under artificial lighting, which lacks bands beneficial to human health, and long-term exposure will have a negative impact on bone health. Here, we report the effects of long-term, low-dose ultraviolet (UV) supplementation to white light-emitting diode (LED) light exposure on intestinal microorganisms and bone metabolism, as well as the correlations between the two. Normal and ovariectomized rats were irradiated with LED white light with or without supplementation with UV. The effects of UV supplementation on the intestinal flora and the relationship between the intestinal flora and bone were investigated by measuring the intestinal flora, bone metabolism markers, and bone histomorphology. UV supplementation affected the bone density and bone mass by changing the relative content of Firmicutes, Saccharibacteria, and Proteobacteria; however, the intestinal flora were not the only factors affecting bone. Ultraviolet supplementation changed the composition and function of the gut flora in the bone loss model. By increasing the synthesis of short-chain fatty acids and affecting immunomodulatory, intestinal flora directly or indirectly regulate the activity of osteoclasts and thus mediate UV-mediated improvements in bone metabolism. Our work shows that UV supplementation affects bone density by influencing the intestinal flora, introducing a novel strategy to develop healthier artificial light sources and prevent bone loss. KEY POINTS: • We measured the bone metabolism markers and bone histomorphometry of rats. • The diversity, composition, and function of intestinal flora were analyzed. • The relationship between gut microbiota and host bone physiology was analyzed.

Oral Microbial Diversity Formed and Maintained through Decomposition Product Feedback Regulation and Delayed Responses.

Oral microbial diversity plays an important role on oral health maintenance. However, there are only few kinds of substrates available for the microbial flora in oral cavity, and it still remains unclear why oral microbial diversity can be formed and sustained without obvious competitive exclusion. Based on experimental phenomena and data, a new hypothesis was proposed, namely, the decomposition product negative feedback regulation on microbial population size and microbial delay responses including reproductive, reaction, interspecific competition, and substrate decomposition delay responses induced by oral immunity. According to hypothesis and its cellular automata (CA) model, the CA simulation results sufficiently proved that the decomposition product negative feedback regulation and four microbial delay responses could significantly alleviate the interspecific competitions and inhibit the emergence of dominant species, causing the formation and sustenance of oral microbial diversity. This study could also offer effective guidance of prevention and treatment of oral cavity diseases.

Gut microbiome-mediated changes in bone metabolism upon infrared light exposure in rats.

Adequate sunlight exposure helps reduce bone loss and is important to bone health. Currently, about 90% of the world population spends a major portion of daily life under artificial lighting. Unlike sunlight, LED white light, the main source of artificial lighting, has no infrared radiation, which is known to be beneficial to human health. In artificial lighting environments, infrared supplementation may be used to simulate the effects of sunlight on bone metabolism. Here, we supplemented white LED exposure with infrared light in normal and ovariectomized rats for three consecutive months and examined bone turnover, bone mass, and bone density. We also analyzed the structure and function of gut microbiota in the rats. Infrared supplementation significantly reduced the abundance of Saccharibacteria and increased the abundance of Clostridiaceae 1 and Erysipelotrichaceae bacteria. Our results indicate that changes in the gut microbiome correlate well with bone mass and bone metabolism. Our work demonstrates that infrared supplementation can have a positive effect on rat bone metabolism by affecting gut microbiota. Our findings will be important considerations in the future design of healthy lighting environments that prevent or possibly ameliorate osteoporosis.