Uric acid-lowering effect of harpagoside and its protective effect against hyperuricemia-induced renal injury in mice.

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

Hematopoietic stem cell (HSC) surface markers improve the understanding of cell identity and function. Here, we report that human HSCs can be distinguished by their expression of the CEA Cell Adhesion Molecule 5 (CEACAM5, CD66e), which serves as a marker and a regulator of HSC function. CD66e+ cells exhibited a 5.5-fold enrichment for functional long term HSCs compared to CD66e- cells. CD66e+CD34+CD90+CD45RA- cells displayed robust multi-lineage repopulation and serial reconstitution ability in immunodeficient mice compared to CD66e-CD34+CD90+CD45RA-cells. CD66e expression also identified almost all repopulating HSCs within the CD34+CD90+CD45RA- population. Together, these results indicated that CEACAM5 is a marker that enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment.

GCH1 reduces LPS-induced alveolar macrophage polarization and inflammation by inhibition of ferroptosis.

OBJECTIVE: GTP cyclohydrolase 1(GCH1) was reported to protect against ferroptosis. However, it is not clear whether GCH1 reduced lipopolysaccharide (LPS)-induced macrophage polarization and inflammation by inhibition of ferroptosis. METHODS: Bioinformatics analysis was used to screen differential expression genes (DEGs) and obtain the different pathways and biological features. Lasso cox regression analysis with ferroptosis related DEGs was established to screen the most relevant genes for disease risk. LPS induced Raw264.7 macrophage polarization model and GCH1-specific siRNA oligos transfection were performed to confirm the function of GCH1. Immunofluorescence staining, western blot and quantitative real-time PCR were performed to detect the expression of iNOS, CD206, GCH1, IL6, SLC2A6, F4/80, IL1ß, TNFα, IL10, GPX4, ACSL4, AMPK and p-AMPK in macrophages. The levels of ROS, SOD, MDA and GSH were detected according to the instructions of the reagent kit, respectively. RESULTS: 542 DEGs were screened from GSE40885 microarray. GO and KEGG pathway enrichment analysis showed that the upregulated DEGs induced by LPS in alveolar macrophage were closely associated with inflammatory and immune responses, the downregulated DEGs were related to lipid metabolism, insulin resistance and AMPK signal pathway. Lasso cox regression analysis screened GCH1, IL6, and SLC2A6. Our experimental results showed that the expression of GCH1 and IL6 in the LPS group was higher than that in the control group, but there was no difference in the expression of SLC2A6. Bioinformatics analysis with GSE112720 observed that ferroptosis was enriched in GCHfl/fl + LPS group compared with GCHfl/flTie2cre + LPS group and GCHfl/fl + control group. Silence of GCH1 increased the levels of IL6, TNF-α and IL-1ß and decreased IL10 level. Silence of GCH1 increased iNOS level and decreased CD206 level. Moreover, silence of GCH1 raised ferroptosis induced by LPS in macrophages and suppressed the activity of AMPK pathway. CONCLUSIONS: GCH1 inhibited ferroptosis in LPS-stimulated macrophages, reduced macrophage toward to M1 polarization and inflammatory response.

JMJD2D stabilises and cooperates with HBx protein to promote HBV transcription and replication.

Background & Aims: HBV infection is a global health burden. Covalently closed circular DNA (cccDNA) transcriptional regulation is a major cause of poor cure rates of chronic hepatitis B (CHB) infection. Herein, we evaluated whether targeting host factors to achieve functional silencing of cccDNA may represent a novel strategy for the treatment of HBV infection. Methods: To evaluate the effects of Jumonji C domain-containing (JMJD2) protein subfamily JMJD2A-2D proteins on HBV replication, we used lentivirus-based RNA interference to suppress the expression of isoforms JMJD2A-2D in HBV-infected cells. JMJD2D-knockout mice were generated to obtain an HBV-injected model for in vivo experiments. Co-immunoprecipitation and ubiquitylation assays were used to detect JMJD2D-HBx interactions and HBx stability modulated by JMJD2D. Chromatin immunoprecipitation assays were performed to investigate JMJD2D-cccDNA and HBx-cccDNA interactions. Results: Among the JMJD2 family members, JMJD2D was significantly upregulated in mouse livers and human hepatoma cells. Downregulation of JMJD2D inhibited cccDNA transcription and HBV replication. Molecularly, JMJD2D sustained HBx stability by suppressing the TRIM14-mediated ubiquitin-proteasome degradation pathway and acted as a key co-activator of HBx to augment HBV replication. The JMJD2D-targeting inhibitor, 5C-8-HQ, suppressed cccDNA transcription and HBV replication. Conclusion: Our study clarified the mechanism by which JMJD2D regulates HBV transcription and replication and identified JMJD2D as a potential diagnostic biomarker and promising drug target against CHB, and HBV-associated hepatocarcinoma. Impact and implications: HBV cccDNA is central to persistent infection and is a major obstacle to healing CHB. In this study, using cellular and animal HBV models, JMJD2D was found to stabilise and cooperate with HBx to augment HBV transcription and replication. This study reveals a potential novel translational target for intervention in the treatment of chronic hepatitis B infection.

Diffuse large B­cell lymphoma and monoclonal gammopathy secondary to immune thrombocytopenic purpura: A case report.

The present study reports the case of a patient with diffuse large B-cell lymphoma (DLBCL) and monoclonal gammopathy (MG) secondary to immune thrombocytopenia purpura (ITP). The clinical diagnoses and investigations of this case are reported. To the best of our knowledge, this is the first study to report DLBCL and MG secondary to ITP. The patient presented with a rare constellation of diseases, which made the diagnosis and treatment difficult for the physicians. The patient was followed up for 10 years using the morphological examination of bone marrow cells after chemotherapy, and currently continues with follow-up examinations. Treatments and prognoses for ITP, DLBCL and MG are common. However, treatments and prognoses are unclear for patients with all three conditions. The different clinical manifestations and disease processes of DLBCL and MG secondary to ITP cause difficulties for physicians in terms of treatment and prognosis. The present case report describes the comprehensive evaluation, diagnosis and treatment of a patient with DLBCL and MG secondary to, and concurrent with, ITP.

LINC00938 alleviates hypoxia ischemia encephalopathy induced neonatal brain injury by regulating oxidative stress and inhibiting JNK/p38 MAPK signaling pathway.

Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death. Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases. LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease. However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway. Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N-acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl2-induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.

Matrine Alleviates Sepsis-Induced Myocardial Injury by Inhibiting Ferroptosis and Apoptosis.

Matrine is a Sophora alkaloid that exerts antitumor effects on a variety of diseases, but few studies have investigated the role of matrine in sepsis-induced myocardial injury. In the present study, we investigated the effects of matrine on septic myocardial injury and the potential mechanisms. Network pharmacology approaches were used to predict the targets of matrine in the treatment of sepsis-induced myocardial injury. A mouse sepsis-induced myocardial injury model was established to determine the effect of matrine. Mouse cardiac function was evaluated by ultrasonography, and cardiac morphology and cardiomyocyte apoptosis were evaluated by HE and TUNEL staining. Oxidative stress was assessed by measuring ROS levels and MDA and SOD activity. Bax, Bcl2, GPX4, ACSL4, PI3K, and AKT protein levels were evaluated by immunohistochemical staining and western blotting. Bioinformatics analysis identified that the potential therapeutic effect of matrine on sepsis-induced myocardial injury is closely related to ferroptosis and apoptosis regulation and showed significant involvement of the PI3K/AKT signaling pathway. In vivo, the matrine group showed improved myocardial function, morphology, and apoptosis ratio and alleviated oxidative stress compared with the LPS group, whereas 25 mg/kg matrine exerted the optimal inhibitory effect. Matrine alleviated LPS-induced cardiomyocyte ferroptosis and apoptosis, resulting in upregulation of Bax/Bcl2 and GPX4 expression and downregulation of ferroptosis marker protein (ACSL4) expression, as shown by immunohistochemistry and western blotting. Moreover, matrine increased PI3K/AKT pathway-related molecule expression and thus modulated ferroptosis and apoptosis. Matrine regulates PI3K/AKT pathway activity to inhibit apoptosis and ferroptosis and thereby alleviates sepsis-induced myocardial injury.

MiR-18a-5p aggravates homocysteine-induced myocardial injury via autophagy. / MiR-18a-5pé€šè¿‡ä»‹å¯¼è‡ªå™¬åŠ é‡åŒåž‹åŠèƒ±æ°¨é ¸è¯±å¯¼çš„å¿ƒè‚ŒæŸä¼¤.

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS: MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.

The dichloromethane extract of Callicarpa longissima rich in diterpenoid phenols exerts anti-inflammatory effect via inhibiting the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa longissima is a typical Yao ethnomedicine that has been used to treat arthritis in China. Our previous study found that the dichloromethane extract (DCME) of C. longissima showed anti-inflammatory activity in vitro. However, the anti-inflammatory mechanism and detailed chemical composition of DCME remain unclear, which lead to the original interest of this study. AIM OF THE STUDY: The study aimed to evaluate the anti-inflammatory properties of the DCME from C. longissima and further explore the accurate chemical components responsible for this active extract. MATERIALS AND METHODS: The anti-inflammatory activity of DCME in vivo was tested with carrageenan-induced mice paw edema model. Its anti-inflammatory mechanism was explored with LPS-stimulated RAW264.7 macrophages model. The compounds in DCME were isolated by repeated column chromatography and their structures were identified on the basis of nuclear magnetic resonance spectroscopy. The anti-inflammatory activities of the isolates in vitro were also tested by suppressing releases of inflammatory mediators (NO, IL-6 and TNF-α) in RAW264.7 macrophages model. In addition, the molecular docking analysis, which evaluated the potential interaction between the compounds and Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB), was performed. RESULTS: DCME effectively alleviated the mice paw edema induced by carrageenan. In LPS-stimulated RAW264.7 cells, DCME significantly decreased the production of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) via inhibiting their mRNA transcription, down-regulated the expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of alpha inhibitor of NF-κB (IκBα), NF-κB p65, and degradation of IκBα. Twelve diterpenoid phenols were identified from DCME, and they not only showed different inhibitory effects on the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells, but also could bind to TLR4 and NF-κB as analyzed by molecular docking. CONCLUSIONS: Taken together, DCME from C. longissima could inhibit inflammatory response both in vitro and in vivo, which is mainly attributed to the synergistic effect of abundant diterpenoid phenols through inhibiting the TLR4/NF-κB signaling pathway, and might be a promising agent for the treatment of inflammatory diseases.

Information disclosure to cancer patients in Mainland China: A meta-analysis.

OBJECTIVE: This study aims to systematically examine Chinese cancer patients' and families' preferences for information disclosure to the patient, patient awareness, and predictors of patient awareness. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Web of Science, Scopus, Proquest, Taylor & Francis Online, and China National Knowledge Infrastructure were searched in April 2022 and Chinese Biomedical Literature Database in July 2022 for quantitative studies. The Mixed Methods Appraisal Tool was used for quality assessment. RESULTS: A total of 22 studies were included, and the average quality score was 0.65/1. Meta-analyses showed that 89.6% and 81.8% of cancer patients wanted to know their diagnosis and prognosis, respectively. Meanwhile, 50.0% and 32.4% of families prefer diagnosis disclosure and prognosis disclosure to the patient, respectively. Significantly more patients than families favored disclosure to the patient. In reality, only 59.3% of cancer patients know their diagnosis, and 19.9% know their prognosis. For predictors, while patients' gender, cancer type (breast cancer or not), treatment method (operation or other), or complications (yes or no) do not influence diagnosis awareness, being younger, being married, having higher educational attainment, having early-stage rather than late-stage cancer, and being in a higher-grade hospital all predict better chances of knowing a diagnosis. No study explored predictors of patients' prognosis awareness. The findings did not vary according to publication time or sample size. CONCLUSIONS: Chinese cancer patients are eager to know their diagnosis and prognosis, but families are hesitant about disclosure to the patient, and patients' awareness is low. While cultural, legal, and medical backgrounds lay the foundation for information disclosure in Mainland China, case-by-case practical factors also make a difference.

The mediating role of resilience in the relationship between social support and quality of life among patients after radical cystectomy: A structural equation model analysis.

AIM: This study aimed to examine the relationship between social support and quality of life in urostomy patients and identify the mediating role of resilience in that relationship. DESIGN: A cross-sectional design. METHODS: Participants included 232 patients who were recruited from a tertiary hospital in Beijing during March 2020 and August 2020. They completed questionnaires about perceived social support, resilience and ostomy-related quality of life. Structural equation modelling was performed to analyse the data. RESULTS: The mean age of patients was 65.79 (SD = 8.67) years, and the mean length of time after surgery was 42.14 (SD = 15.76) months. Urostomy patients' quality of life, social support and resilience were all above moderate. Social support had a positive direct effect on the quality of life and a positive indirect effect on the quality of life through the mediating role of resilience.

LncRNA SLC7A11-AS1 stabilizes CTCF by inhibiting its UBE3A-mediated ubiquitination to promote melanoma metastasis.

Malignant melanoma (MM) is one of the most aggressive types of skin cancer. Long non-coding RNAs (lncRNAs) are important regulatory factors in the pathogenesis of various diseases. Here, we found that the lncRNA SLC7A11-AS1 was highly expressed in MM. Therefore, we investigated its regulatory role in the migration and invasion of MM cells and the associated mechanism. SLC7A11-AS1 and CTCF levels in MM cell lines were detected using RT-qPCR and western blotting, and their regulatory effects on the migratory and invasive abilities were determined using CCK-8, EdU, transwell, wound-healing assays and mouse model. RNA pull-down and RIP assays were performed to explore the association of SLC7A11-AS1 and CTCF and the correlation between CTCF and UBE3A. SLC7A11-AS1 and CTCF were highly expressed in MM cells. The knockdown of SLC7A11-AS1 decreased the expression of CTCF. Mechanistically, SLC7A11-AS1 inhibited the degradation of CTCF by inhibiting the ubiquitination by UBE3A. The knockdown of both SLC7A11-AS1 and CTCF inhibited the migration and invasion of MM cells and attenuated MM-to-lung metastasis in a mouse model. Taken together, SLC7A11-AS1 promoted the invasive and migratory abilities of MM cells by inhibiting the UBE3A-regulated ubiquitination of CTCF. Therefore, SLC7A11-AS1 may be a potential therapeutic target for MM.

Comparison of anxiety and depressive symptoms of head and neck cancer patients in a closed-loop management system before and during the 2019 coronavirus pandemic: a comparative study.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) poses an unprecedented challenge to health and the financial system, especially the healthcare of patients with cancer. However, the research on the negative effect of the pandemic on the anxiety and depressive symptoms of cancer patients in closed-loop is rarely reported at present. In view of the limitations of previous studies. In this study, we compared the anxiety and depressive symptoms of head and neck cancer patients in the closed-loop management system before and during the 2019 coronavirus pandemic. METHODS: In this comparative study, a total of 526 head and neck cancer patients (269 and 257 patients before and during the COVID-19 pandemic) were enrolled in the present study. The two groups of patients' median age (53 years, 52 years), female distribution (70.26%, 66.15%) and male distribution (29.74%, 33.85%) were analyzed before and after the COVID-19 epidemic. They received questionnaires using the standardized data forms of Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) to collect the relevant data of patients for retrospective investigation. For data analysis, either the chi-squared test or Fisher's exact test was employed for categorical variables, and we described the time trend of psychological states before and after the outbreak with Cochran-Armitage trend (CAT) test. RESULTS: A total of 526 head and neck cancer patients were included in the final analysis; 26.85% and 50.19% of cases experienced anxiety and depression during the COVID-19 epidemic. In contrast, 18.22% and 33.46% of cases had experienced anxiety and depression before the pandemic. According to the statistical results, the prevalence of anxiety and depression in patients during the COVID-19 epidemic was higher compared to that of patients prior to the pandemic (P=0.018). More importantly, both anxiety and depression incidence trends increased significantly before and after the outbreak of COVID-19 (P=0.000). CONCLUSIONS: The present study demonstrates the significant impact of COVID-19 on the psychological states of cancer patients in the case of closed-loop management system, effectively indicating the need for appropriate changes in treatment decisions, enhanced psychotherapy, and interventions to reduce the incidence of anxiety, depression, and even suicide during this pandemic.

Steroidal saponin components and their cancer cell cytotoxicity from Paris rugosa.

The chemical components and availability of Paris rugosa were investigated for the first time, using a UPLC-MS/MS-based molecular networking strategy and phytochemical research. Ultimately, eleven undescribed steroidal saponins, parisrugosides A-K, and ten known analogs were identified. Their structures were confirmed using comprehensive spectroscopic data and chemical methods. The aglycones of parisrugosides A-D are first spirostanes with an epoxy group at C-5/C-6, a hydroxy group at C-7, and a double bond at C-8/C-9 or C-8/C-14. Parisrugosides G and H possess an undescribed spirostane aglycone with two double bonds located at C-5/C-6 and C-8/C-9, which are conjugated with a carbonyl group at C-7. The isolates were evaluated for their cytotoxicity against five human cancer cell lines (human HL-60 leukemia, A549 lung, MCF-7 breast, SMMC-7721 liver, and SW480 colon solid cancer cell lines). Parisyunnanoside D, kingianoside K, and dichotomin displayed significant cytotoxicity against these cancer lines, with IC50 values ranging from 0.50 to 19.58 µM.

HuanglianGanjiang Tang alleviates DSS-induced colitis in mice by inhibiting necroptosis through vitamin D receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: HuanglianGanjiang Tang (HGT) is a classic prescription of traditional Chinese medicine (TCM) recorded in Dan Xi Xin Fa, which was used to alleviate manifestations like diarrhea, abdominal pain and hemafecia. In current clinical practices, HGT is adopted for the treatment of ulcerative colitis (UC) and affords good curative effect. However, the underlying mechanism deserves further elucidation. AIM OF THE STUDY: UC is a hard-to-curable and easy-to-recurrent inflammatory disease. This study is to evaluate the potential therapeutics and explore the molecular mechanism of HGT on UC in the mouse model. MATERIALS AND METHODS: The components of HGT extracts were identified by HPLC. The colitis of mice was induced by 3% (w./v.) dextran sulfate sodium (DSS). The HGT decoction was prepared through boiling and centrifuging. The mice were given HGT decoction via oral gavage (0.34 g/ml & 0.68 g/ml; 5 ml/kg b.w.). The protective role of HGT on colitis mice was evaluated by body weight change, colon length, disease activity index (DAI) and histological scores. The expressions of necroptosis-related and vitamin D receptor (VDR)-related proteins were measured by Western blot, RT-qPCR and immunofluorescence. RESULTS: HGT could significantly reduce the loss of body weight and colon length in colitis mice, and alleviated the DAI and histological scores. Mechanically, HGT also promoted the expression of E-cadherin, Occludin, ZO-1 and VDR, and reduced the level of intestinal inflammatory cytokines, such as, IL-6, IL-1ß and TNF-α. Besides, HGT downregulated the protein level of p-RIPK3, p-RIPK1 and p-MLKL while upregulated the protein level of Caspase-8 in colon tissue compared to the model group. CONCLUSION: Our study addressed that HGT can alleviate DSS-induced colitis of mice through inhibiting colonic necroptosis by upregulating the level of VDR.

Naphthoquinones from Catalpa bungei "Jinsi" as potent antiproliferation agents inducing DNA damage.

Structure-guided isolation of a CH2Cl2-soluble fraction of the heartwood of Catalpa bungei "Jinsi" provided two new naphthoquinones, 9-hydroxy-4-oxo-α-lapachone (1) and 6-hydroxy-4-oxo-α-lapachone (2), together with three undescribed ones (3-5) and six known ones (6-11). The structures were elucidated on the basis of spectroscopic methods including electronic circular dichroism calculation. The antiproliferative effects of these isolates were evaluated in human breast adenocarcinoma cells MCF7. (4R)-4,9-dihydroxy-α-lapachone (5) and (4S)-4,9-dihydroxy-α-lapachone (6) exhibited the significant activities with IC50 values of 2.19 and 2.41 µM, respectively. The structure-activity relationship of 1-11 in the antiproliferative assay was then discussed. The most potent 5 and 6 were found to induce cell arrest in G1 phage through DNA damage. The findings provided some valuable insights for the discovery and structural modification of α-lapachone as antiproliferative lead compounds against human breast adenocarcinoma cells.

Parisfargosides A-E, five new cholestane glycosides from the rhizomes of Paris fargesii.

Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, ß-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridine­d5 and DMSO­d6 as solvents. In addition, the platelet aggregation activity and cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480) of compounds 1-5 were evaluated.

Case Report: A Case of Hailey-Hailey Disease Mimicking Condyloma Acuminatum and a Novel Splice-Site Mutation of ATP2C1 Gene.

Hailey-Hailey disease (HHD) is a rare autosomal-dominant blistering disorder characterized by recurrent vesicular and erosive lesions at intertriginous sites. We described a 24-year-old male who presented with multiple bright red verrucous papules in his mons pubis, bilateral groins, scrotum, perineum, and crissum, clinically resembling condyloma acuminatum. The histopathology showed extensive acantholysis with the characteristic appearance of a dilapidated brick-wall. The mutation analysis revealed a novel splice-site mutation in the ATP2C1 gene. The patient was definitely diagnosed with HHD. The antibacterial treatments resulted in a dramatic improvement. Our findings help to broaden the understanding of clinical manifestations of HHD and improve the clinical diagnosis and treatment of this disease.

Hsp22 ameliorates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidative stress, and apoptosis.

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1ß, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.