The lack of PPARα exacerbated the progression of non-alcoholic steatohepatitis in mice with spleen deficiency syndrome by triggering an inflammatory response.

Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders.

Naringin is a natural flavonoid with therapeutic properties found in citrus fruits and an active natural product from herbal plants. Naringin has become a focus of attention in recent years because of its ability to actively participate in the body's immune response and maintain the integrity of the immune barrier. This review aims to elucidate the mechanism of action and therapeutic efficacy of naringin in various inflammatory diseases and to provide a valuable reference for further research in this field. The review provided the chemical structure, bioavailability, pharmacological properties, and pharmacokinetics of naringin and found that naringin has good therapeutic potential for inflammatory diseases, exerting anti-inflammatory, anti-apoptotic, anti-oxidative stress, anti-ulcerative and detoxifying effects in the disease. Moreover, we found that the great advantage of naringin treatment is that it is safe and can even alleviate the toxic side effects associated with some of the other drugs, which may become a highlight of naringin research. Naringin, an active natural product, plays a significant role in systemic diseases' anti-inflammatory and antioxidant regulation through various signaling pathways and molecular mechanisms.

Purification, Structural Analysis and Cardio-Protective Activity of Polysaccharides from Radix Astragali.

Two polysaccharides, named APS2-I and APS3-I, were purified from the water extract of Radix Astragali. The average molecular weight of APS2-I was 1.96 × 106 Da and composed of Man, Rha, GlcA, GalA, Glc, Gal, Xyl, and Ara in a molar ratio of 2.3:4.8:1.7:14.0:5.8:11.7:2.8:12.6, while the average molecular weight of APS3-I was 3.91 × 106 Da and composed of Rha, GalA, Glc, Gal, and Ara in a molar ratio of 0.8:2.3:0.8:2.3:4.1. Biological evaluation showed APS2-I and APS3-I had significant antioxidant activity and myocardial protection activity. Furthermore, total polysaccharide treatment could significantly enhance hemodynamic parameters and improve cardiac function in rat ischemia and reperfusion isolated heart models. These results provided important information for the clinical application of APS in the field of cardiovascular disease and implied that Astragalus polysaccharides (APS) could be considered as a reference for the quality control of Radix Astragali.

A herbal product inhibits carbon tetrachloride-induced liver fibrosis by suppressing the epidermal growth factor receptor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Huayu formula (FZHY), composed of Salvia miltiorrhiza Bunge, Cordyceps sinensis, the seed of Prunus persica (L.) Batsch, the pollen of Pinus massoniana Lamb, Gynostemma pentaphyllum (Thunb.) Makino and the fruit of Schisandra chinensis (Turcz.) Baill, is a Chinese herbal compound with demonstrated clinical benefits in liver fibrosis (LF). However, its potential mechanism and molecular targets remain to be elucidated. AIM OF THE STUDY: This study was designed to evaluate the anti-fibrotic role of FZHY in hepatic fibrosis and to elucidate the potential mechanisms. MATERIALS AND METHODS: Network pharmacology was assayed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-LF. Then the core pharmaceutical target for FZHY against LF was verified by serum proteomic analysis. Further in vivo and in vitro assays were performed to verify the prediction of the pharmaceutical network. RESULTS: The network pharmacology analysis revealed that a total of 175 FZHY-LF crossover proteins were filtered into a protein-protein interaction (PPI) network complex and designated as the potential targets of FZHY against LF, and the Epidermal Growth Factor Receptor (EGFR) signaling pathway was further explored according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then analytical studies were validated by carbon tetrachloride (CCl4)-induced model in vivo. We found FZHY could attenuate CCl4-induced LF, especially decrease p-EGFR expression in α-Smooth Muscle Actin (α-SMA)-positive hepatic stellate cell (HSC) and inhibit the downstream of the EGFR signaling pathway, especially Extracellular Regulated Protein Kinases (ERK) signaling pathway in liver tissue. We further demonstrate that FZHY could inhibit Epidermal Growth Factor (EGF)-induced HSC activation, as well as the expression of p-EGFR and the key protein of the ERK signaling pathway. CONCLUSIONS: FZHY has a good effect against CCl4-induced LF. The action mechanism was associated with the down-regulation of the EGFR signaling pathway in activated HSCs.

A robust and ultra-high-surface hydrogen-bonded organic framework promoting high-efficiency solid phase microextraction of multiple persistent organic pollutants from beverage and tea.

Persistent organic pollutants (POPs) are widely distributed in the environment and are toxic, even at low concentrations. In this study, we first used hydrogen-bonded organic framework (HOF) to enrich POPs, based on solid phase microextraction (SPME). The HOF called PFC-1 (self-assembled by 1,3,6,8-tetra(4-carboxylphenyl)pyrene) has an ultra-high specific surface area, excellent thermochemical stability, and abundant functional groups, making it potential to be an excellent coating in SPME. And the as-prepared PFC-1 fiber have demonstrated outstanding enrichment abilities for nitroaromatic compounds (NACs) and POPs. Furthermore, the PFC-1 fiber was coupled with gas chromatography-mass spectrometry (GC-MS) to develop an ultrasensitive and practical analytical method with wide linearity (0.2-200 ng·L-1), low detection limits for organochlorine pesticides (OCPs) (0.070-0.082 ng·L-1) and polychlorinated biphenyls (PCBs) (0.030-0.084 ng·L-1), good repeatability (6.7-9.9%), and satisfactory reproducibility (4.1-8.2%). Trace concentrations of OCPs and PCBs in drinking water, tea beverage, and tea were also determined precisely with the proposed analytical method.

Lupus Recipe inhibits cGVHD-induced lupus nephritis in mice and promote renal LC3-associated autophagy.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well-established model of SLE. LC3-associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3-associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3-associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD-induced LN, which may attribute to the increased levels of LC3-associated autophagy.

The clinical diagnostic value of plasma miR-592 and miR-217-3p levels in retinoblastoma.

Background: This study was designed to investigate the abnormal expression of plasma miR-592 and miR-217-3p in retinoblastoma (Rb) and explore the clinical diagnostic value of their expression levels for Rb. Methods: The 100 Rb patients who came to Nanchang Hongdu Hospital of Traditional Chinese Medicine from January 2018 to January 2019 were selected as the Rb group, and 100 healthy patients who came to the physical examination centre during the same period were selected as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression levels of plasma miR-592 and miR-217-3p in all subjects; analyse the relationship between plasma miR-592 and miR-217-3p levels and the clinicopathological characteristics of Rb. Pearson correlation analysis evaluated the relationship between plasma miR-592 and miR-217-3p levels and overall survival. Results: Plasma levels of miR-592 and miR-217-3p in the Rb group were significantly higher than those in the control group (p<0.0001), and the expression of miR-592 was significantly correlated with family genetic history (p 0.0001), tumour bias (p=0.0081), lymph node metastasis (p=0.0048) and pathological grade (p=0.0025), and the expression of miR-217-3p was significantly related to family genetic history (p 0.0001), optic nerve infiltration (p 0.0001), lymph node metastasis (p=0.0090), and pathological grade (p 0.0001). The high expression of miR-592 and miR-217-3p presents a more serious pathological manifestation of Rb, and the overall survival of patients is significantly shortened with the increase of miR-592 (r=-0.2276, p=0.0052) and miR-217-3p levels (r=-0.6461, p 0.0001). Conclusions: and miR-217-3p are highly expressed in the plasma of Rb patients, and their elevated levels present severe pathological manifestations of Rb and shortened overall survival, which is expected to become biomarkers for clinical diagnosis of Rb.

[Responses of soil microbial carbon use efficiency to short-term nitrogen addition in Castanopsis fabri forest]. / ç½—æµ®æ ²æž—åœŸå£¤å¾®ç”Ÿç‰©ç¢³åˆ©ç”¨æ•ˆçŽ‡å¯¹çŸ­æœŸæ°®æ·»åŠ çš„å“åº”.

As an important parameter regulating soil carbon mineralization, microbial carbon use efficiency (CUE) is essential for the understanding of carbon (C) cycle in terrestrial ecosystems. Three nitrogen supplemental levels, including control (0 kg N·hm-2·a-1), low nitrogen (40 kg N·hm-2·a-1), and high nitrogen (80 kg N·hm-2·a-1), were set up in a Castanopsis fabri forest in the Daiyun Mountain. The basic physical and chemical properties, organic carbon fractions, microbial biomass, and enzyme activities of the soil surface layer (0-10 cm) were measured. To examine the effects of increasing N deposition on microbial CUE and its influencing factors, soil microbial CUE was measured by the 18O-labelled-water approach. The results showed that short-term N addition significantly reduced microbial respiration rate and the activities of C and N acquisition enzymes, but significantly increased soil microbial CUE. ß-N-acetyl amino acid glucosidase (NAG)/microbial biomass carbon (MBC), microbial respiration rate, ß-glucosidase (BG)/MBC, cellulose hydrolase (CBH)/MBC, and soil organic carbon content were the main factors affecting CUE. Moreover, CUE significantly and negatively correlated with NAG/MBC, microbial respiration rate, BG/MBC, and CBH/MBC, but significantly and positively correlated with soil organic carbon. In summary, short-term N addition reduced the cost of soil microbial acquisition of C and N and microbial respiration, and thus increased soil microbial CUE, which would increase soil carbon sequestration potential of the C. fabri forest.

Salvia miltiorrhiza in thorax and abdomainal organ fibrosis: A review of its pharmacology.

Organ fibrosis is a common pathological change that finally results in organ failure, which involves the destruction of parenchyma cells, the activation of mesenchymal cells and the imbalance of immunological cells. In recent years, although some breakthroughs have been made in understanding the pathogenesis and therapeutics of organ fibrosis, no registered drugs could directly target the fibrotic process, which constitutes a major biomedical challenge. Salvia miltiorrhiza (SM) is a well-known medicinal plant in China, which has been widely applied because of its pharmacological effects on anti-oxidative, anti-myocardial infarction, anti-fibrotic, anti-inflammatory, and anti-neoplastic properties. Accumulated evidence suggested that SM played critical roles against organ fibrosis in vivo and in vitro experiments by its multiple biological compounds. In this review, we discussed the recent advances on the phytochemistry and pharmacological mechanisms of SM and its active ingredients in liver, lung, kidney, and heart fibrosis, which might help to promote the treatment of fibrotic diseases in thorax and abdomainal viscera in clinic.

Network Pharmacology-Based Prediction and Pharmacological Validation of Effects of Astragali Radix on Acetaminophen-Induced Liver Injury.

Astragali Radix (AR) has been widely used in traditional Chinese medicine prescriptions for acute and chronic liver injury. However, little is known about the effects of AR on acetaminophen (APAP)-induced liver injury (ALI). In the current study, a network pharmacology-based approach was applied to characterize the action mechanism of AR on ALI. All compounds of AR were obtained from the corresponding databases, and active compounds were selected according to its oral bioavailability and drug-likeness index. The potential genes of AR were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) and PubChem, whereas the potential genes related to ALI were obtained from Online databases (GeneCards and Online Mendelian Inheritance in Man) and Gene Expression Omnibus profiles. The enriched processes, pathways, and target genes of the diseases were analyzed by referring to the Search Tool for the Retrieval of Interacting Genes/Proteins database. A network constructed through Cytoscape software was used to identify the target proteins that connected the compounds in AR with the differential genes of ALI. Subsequently, the potential underlying action mechanisms of AR on ALI predicted by the network pharmacology analyses were experimentally validated in APAP-induced liver injury in mice and HL7702 cells incubated with APAP. The compound-target network included 181 targets, whereas the potential genes related to ALI were 4,621. A total of 49 AR-ALI crossover proteins, corresponding to 49 genes, were filtered into a protein-protein interaction network complex and designated as the potential targets of AR on ALI. Among the genes, the three highest-scoring genes, MYC, MAPK8, and CXCL8 were highly associated with apoptosis in ALI. Then in vitro and in vivo experiments confirmed that AR exhibited its prominent therapeutic effects on ALI mainly via regulating hepatocyte apoptosis related to inhibiting the expressions of MYC (c-Myc), MAPK8 (JNK1), and CXCL8 (IL-8). In conclusion, our study suggested that the combination of network pharmacology prediction with experimental validation might offer a useful tool to characterize the molecular mechanism of AR on ALI.

[Effects of shell composition in shell-core structured nanoparticles on oral physiological barrier and bioavailability].

The present study prepared shell-core nanoparticles comprising poly(lactic-co-glycolic acid)(PLGA) cores encapsulated by shells composed of mixed lipids(Lipoid S100 and DSPE-PEG 2000) or polymer F127 to investigate the effects of shell composition on overcoming physiological barriers of gastrointestinal mucus and intestinal epithelial cells and improving bioavailability.The results are expected to provide references for the research on the improvement of the oral bioavailability of Chinese medicine by nanocar-riers. Silibinin(SLB) was used as a model drug to prepare PLGA nanoparticles coated with the shell of mixed lipids(SLB-LPNs) or F127(SLB-FPNs) via a modified nanoprecipitation method.Transmission electron microscopy showed that both LPNs and FPNs were spherical with a core-shell structure.The average particle sizes of SLB-LPNs and SLB-FPNs were(94.13±2.23) and(95.42±4.91) nm, respectively.The Zeta potential values were(-39.3±2.8) and(-17.0±0.2) mV, respectively.X-ray diffraction analysis revealed the presence of SLB in the two types of nanoparticles in a molecular or amorphous state.The ability of nanoparticles to cross both the mucus and epithelial barriers were evaluated using the cellular internalization kinetics assay.LPNs showed a higher rate of cell internalization than FPNs, indicating that LPNs could penetrate the mucus layer and become internalized by cells more rapidly.As revealed by the in vivo pharmacokinetic assay in rats with SLB suspension as the reference, the relative oral bioavailability of SLB-LPNs and SLB-FPNs was 400.37% and 923.31%, respectively.The effect of SLB-FPNs in improving oral bioavailability was more significant than that of SLB-LPNs.In summary, shell composition can influence the ability of nanoparticles to overcome oral physiological bar-riers, such as the mucus layer and intestinal epithelial cells, and improve oral bioavailability.Shell-core structured nanoparticles are promising nanocarriers for oral drug delivery systems.

[Action mechanism and active components of Fuzheng Huayu Recipe against liver fibrosis via regulating macrophage with network pharmacology and transcriptomics methods].

We have demonstrated that Fuzheng Huayu Recipe(FZHY) plays an anti-liver fibrosis role by regulating the polarization of intrahepatic macrophages, while the key targets in macrophages and the effective components of FZHY remain unclear. In this study, we obtained the potential anti-liver fibrosis target set of FZHY through network pharmacological analysis, and the differentially expressed gene set of FZHY for the prevention and treatment of mouse liver fibrosis through RNA-Seq of the liver tissue. The potential core targets of FZHY against liver fibrosis were obtained by degree value analysis of the common target proteins between the above two sets. Then, through the retrieval of PubMed database, we identified the potential key targets in macrophages. After that, the effective components in FZHY corresponding to key targets were obtained by reverse pharmacological analysis. Finally, we verified the regulatory effects of these effective components on the expression of key target genes by using the lipopolysaccharide-induced M1 macrophages derived from THP-1 cells. The RNA-Seq data combined with network pharmacological analysis showed that FZHY might alleviate liver fibrosis by regulating the expression of CCL2, TIMP1, and MMP2 genes in macrophages. The results of in vivo experiments showed that FZHY significantly inhibited the expression of CCL2 and TIMP1 genes and promoted the expression of MMP2 genes in liver tissues of liver fibrosis mice. The results of in vitro experiments demonstrated that FZHY and its four effective components(luteolin, ursolic acid, quercetin, and danshensu) significantly inhibited the expression of CCL2 and TIMP1 genes in M1 macrophages derived from THP-1 cells. In addition, the expression of MMP2 gene was up-regulated by luteolin, ursolic acid, and quercetin, not affected by FZHY, and down-regulated by danshensu. FZHY could inhibit the expression of CCL2 and TIMP1 genes in M1 macrophages by the four effective components to achieve the anti-inflammatory and anti-liver fibrosis effects.

An Herbal Product Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice via Regulating NF-κB/TNF-α Signaling in Macrophages.

Background and aim: Pro-inflammatory macrophages aggravated progress of pulmonary fibrosis (PF) both in patients and animal models. Fuzheng Huayu (FZHY) formula, a Chinese herbal product, is effective in treating pulmonary fibrosis in our previous study. But its action mechanism against PF relating to macrophage activation was unclear. This study was designed to evaluate the anti-fibrotic and anti-inflammatory roles of FZHY in pulmonary fibrosis and to elucidate the potential mechanisms. Methods: Network pharmacology was employed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-pulmonary fibrosis. According to the data of bioinformatics analysis, the key pharmacological target for FZHY against PF was screened. The network pharmacological prediction was validated by a series of experimental assays, including CCK8, western blot and immunofluorescence staining. Then molecular mechanism of FZHY on relating to the predictive target were studied in bleomycin induced pulmonary fibrosis in mice with methylprednisolone as a positive control, and in lipopolysaccharide (LPS) stimulated cultured macrophages in culture, respectively. Results: The network pharmacology analysis reveal that a total of 12 FZHY-PF crossover proteins were filtered into a protein-protein interaction network complex and designated as the potential targets of FZHY against pulmonary fibrosis, while TNF-α signal pathway ranked at the top. FZHY and methylprednisolone could attenuate the lung fibrosis and decrease pulmonary TNF-α expression in bleomycin induced fibrotic mice, without difference between two treatments. While TNF-α was mainly originated from macrophages identified by double fluorescent staining of TNF-α and F4/80. LPS stimulated cultured macrophage polarization and activation demonstrated by the enhance contents of TNF-α and iNOS but decreased level of Arg-1. FZHY could alleviate the LPS stimulated macrophage polarization and activation demonstrated by decreasing TNF-α and iNOS and increasing Arg-1. In particular, FZHY could significantly reduce the production of p65 and the nuclear translocation of phosphorylated p65. Conclusion: Fuzheng Huayu formula has a good effect against pulmonary fibrosis induced by bleomycin in mice, whose action mechanism was associated with down-regulation of NF-κB/TNF-α signaling pathway in pro-inflammatory macrophages. These findings provided an important strategy for developing new agents against lung fibrosis and accelerated FZHY product application on patients with lung fibrosis.

Tea polyphenols alleviate the adverse effects of diabetes on oocyte quality.

Maternal diabetes mellitus reduces oocyte quality, such as abnormalities of spindle assembly and chromosome segregation, mitochondrial dysfunction, decrease of fertilization rate, increase of ROS, and so on. So, it is important to research how to restore the decreased oocyte quality induced by maternal diabetes mellitus. Polyphenols are the most abundant bioactive components of green tea. It is reported that tea polyphenols have many health functions, for instance anti-oxidation, anti-inflammation, anti-obesity, and anti-diabetes. Thus, we hypothesize that tea polyphenols may play a crucial role in alleviating adverse effects of diabetes on oocyte quality. In the present study, we researched the effects of tea polyphenols on diabetic oocyte maturation in vitro. Compared with the control, oocytes from diabetic mice displayed a lower maturation rate and a higher frequency of spindle defects and chromosome misalignment. However, tea polyphenols significantly increased the oocyte maturation rate, and reduced the incidence of abnormal spindle assembly and chromosome segregation. Tea polyphenols also obviously decreased the reactive oxygen species (ROS) levels in diabetic oocytes, and increased the expression of antioxidant genes (Sod1 and Sod2). Abnormal mitochondrial membrane potential was also alleviated in diabetic oocytes, and the expression of genes regulating mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1) was significantly increased while tea polyphenols were added. Meanwhile, tea polyphenols reduced DNA damage in diabetic oocytes which may be mediated by the increased expression of Rad51, related to DNA damage repair. Our results suggest that tea polyphenols would, at least partially, restore the adverse effects of diabetes mellitus on oocyte quality.

A Traditional Chinese Medicine for the Treatment of Endometrial Hyperplasia via Regulating the HPO Axis in Rats.

Dysfunctional uterine bleeding, accompanied by endometrial hyperplasia (EH), is a common gynecological disease that seriously affects female physical and mental health. Some drugs have been prompted to cure the disease, but most medications have certain side effects and limitations. In the present study, we demonstrated an unexploited Chinese traditional medicine, a combination of Saururus chinensis, Celosia cristata, and Spatholobus suberectus (SCS), which could be used for the treatment of EH and associated complications in rats. We identified the active components from the three Chinese herbs via thin-layer chromatography and high-performance liquid chromatography methods. In addition, serum biochemical indexes and histologic section results found that acute high-dose SCS exerted no adverse impacts on the rats. We then showed that SCS shortened coagulation time (p=0.018) and degree of swelling (p=0.021) on rats at 30 min compared to blank control. Further studies proved that recovered endometrial thickness was associated with the modulation of four hormones (follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone). Specifically, follicle-stimulating hormone and progesterone contents increased gradually with time, and estrogen was decreased, whereas luteinizing hormone content was returned to normal after a short-term elevation (p < 0.05). Besides, SCS increased uterine endometrium's mRNA expression levels of matrix metalloproteinase-1 (p < 0.001) and tissue inhibitor of matrix metalloproteinase-1 (p < 0.001), promoting the repair of proliferating endometrium in the rats. Collectively, our study indicates that SCS harbors a profoundly curative effect on the treatment of EH and relative complications and uncovers the mechanism at molecular and gene expression levels.

The prospects of DNA damage repair variants guiding platinum compounds in the treatment of triple negative breast cancer / 中华肿瘤杂志

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.

Risk Factors for Cryptococcal Meningitis Recurrence in Human Immunodeficiency Virus (HIV)-Infected Patients in a Large Chinese Acquired Immune Deficiency Syndrome (AIDS) Treatment Center.

BACKGROUND Cryptococcal meningitis (CM) is one of the most common opportunistic neuroinfections in patients with HIV. Most studies have focused on non-HIV CM and there are only a few studies on HIV CM in China. The purpose of the present study was to evaluate the characteristics and risk factors for CM recurrence in patients infected with HIV in the Chongqing Public Health Treatment Center in China. MATERIAL AND METHODS From January 2014 to December 2017, all patients with CM aged 18 years or older were enrolled and a case-control study was performed to determine the risk factors associated with recurrence of CM. Antimicrobial susceptibility was determined with a fungal drug sensitivity kit and the sequence types (STs) were analyzed with multilocus sequence typing. RESULTS The incidence of CM in the 5185 HIV-infected patients was 3.5% (179). Follow-up data were available for 82 of the patients for whom complete medical records were available and they were included in the present study. There were 7 STs among 82 Cryptococcus neoformans isolates; ST5 and ST31 were the most prevalent genotypes. Testing showed that C. neoformans had high sensitivity to 5 antifungal drugs and no differences in resistance were observed, even when different STs were tested. Risk factors for recurrence were analyzed in 69 patients, excluding those who died. The results of multivariate analysis showed that only hospital stay was associated with recurrence of CM. CONCLUSIONS Our results indicated that combining education about medication with clinical treatment could help prevent recurrence of CM.

Effect of Sutellarin on Neurogenesis in Neonatal Hypoxia-Ischemia Rat Model: Potential Mechanisms of Action.

To investigate the therapeutic efficacy of Scutellarin (SCU) on neurite growth and neurological functional recovery in neonatal hypoxic-ischemic (HI) rats. Primary cortical neurons were cultured to detect the effect of SCU on cell viability of neurons under oxygen-glucose deprivation (OGD). Double immunofluorescence staining of Tuj1 and TUNEL then observed the neurite growth and cell apoptosis in vitro,and double immunofluorescence staining of NEUN and TUNEL was performed to examine the neuronal apoptosis and cell apoptosis in brain tissues after HI in vivo. Pharmacological efficacy of SCU was also evaluated in HI rats by neurobehavioral tests, triphenyl tetrazolium chloride staining, Hematoxylin and eosin staining and Nissl staining. Astrocytes and microglia expression in damaged brain tissues were detected by immunostaining of GFAP and Iba1. A quantitative real-time polymerase chain reaction and western blot were applied to investigate the genetic expression changes and the protein levels of autophagy-related proteins in the injured cortex and hippocampus after HI. We found that SCU administration preserved cell viability, promoted neurite outgrowth and suppressed apoptosis of neurons subjected to OGD both in vitroand in vivo. Meanwhile, 20 mg/kg SCU treatment improved neurological functions and decreased the expression of astrocytes and microglia in the cortex and hippocampus of HI rats. Additionally, SCU treatment depressed the elevated levels of autophagy-related proteins and the p75 neurotrophin receptor (p75NTR) in both cortex and hippocampus. This study demonstrated the potential therapeutic efficacy of SCU by enhancing neurogenesis and restoring long-term neurological dysfunctions, which might be associated with p75NTR depletion in HI rats.