Comparative Analysis of Active Ingredients and Potential Bioactivities of Essential Oils from Artemisia argyi and A. verlotorum.

Artemisia argyi H. Lév. and Vaniot is a variety of Chinese mugwort widely cultured in central China. A. verlotorum Lamotte, another variety of Chinese mugwort, has been used in the southern region of China since ancient times. Despite their similar uses in traditional medicine, little is known about the differences in their active ingredients and potential benefits. Herein, the chemical compositions of the essential oils (EOs) from both varieties were analyzed using chromatography-mass spectrometry (GC-MS). A series of databases, such as the Traditional Chinese Medicine Systems Pharmacology database (TCMSP), SuperPred database and R tool, were applied to build a networking of the EOs. Our results revealed significant differences in the chemical compositions of the two Artemisia EOs. However, we found that they shared similar ingredient-target-pathway networking with diverse bioactivities, such as neuroprotective, anti-cancer and anti-inflammatory. Furthermore, our protein connection networking analysis showed that transcription factor p65 (RELA), phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) and mitogen-activated protein kinase 1 (MAPK1) are crucial for the biological activity of Artemisia EOs. Our findings provided evidence for the use of A. verlotorum as Chinese mugwort in southern China.

Selenium-Enriched Cardamine violifolia Increases Selenium and Decreases Cholesterol Concentrations in Liver and Pectoral Muscle of Broilers.

BACKGROUND: Supernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. OBJECTIVES: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. METHODS: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20-0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver. RESULTS: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4-127% and decreased (P < 0.05) total cholesterol concentrations by 12.5-46.7% and/or triglyceride concentrations by 28.8-31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and ß-oxidation of fatty acid-related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. CONCLUSIONS: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.

Structure-Based Molecular Networking for the Discovery of Anti-HBV Compounds from Saussurea lappa (Decne.) C.B Clarke.

It is a crucial to find target compounds in natural product research. This study presents a concept of structure-guided isolation to find candidate active molecules from herbs. We establish a process of anti-viral sesquiterpene networking. An analysis of the networking suggested that new anti-HBV sesquiterpene may be attributable to eudesmane-, guaiane-, cadinane-, germacane- and bisabolane-type sesquiterpenes. In order to evaluate the efficiency of the structure-based molecular networking, ethanol extract of Saussurea lappa (Decne.) C.B Clarke was investigated, which led to the isolation of two guaiane-type (1 and 14), ten eudesmane-type (2-5 and 8-13), two chain (6 and 7) and one germacrane-type (15) sesquiterpenes, including seven new ones, lappaterpenes A-G (1-7), which are reported on herein. The absolute configurations of the new compounds were established by coupling constants, calculated ECD and ROESY correlations, as well as comparisons of optical rotation values with those of known compounds. The absolute configuration of compound 2 was further confirmed by X-ray diffraction. Compounds 1-15 were evaluated for their potency against hepatitis B virus. Compounds 4, 6, 7 and 9 showed effect on HBsAg with inhibition ratios of more than 40% at 30 µM concentrations. Compounds 14 and 15 inhibited HBsAg secretion with the values of IC50 0.73 ± 0.18 and 1.43 ± 0.54 µM, respectively. Structure-based molecular networking inspired the discovery of target compounds.

Beyond defense: regulation of neuronal morphogenesis and brain functions via Toll-like receptors.

Toll-like receptors (TLRs) are well known as critical pattern recognition receptors that trigger innate immune responses. In addition, TLRs are expressed in neurons and may act as the gears in the neuronal detection/alarm system for making good connections. As neuronal differentiation and circuit formation take place along with programmed cell death, neurons face the challenge of connecting with appropriate targets while avoiding dying or dead neurons. Activation of neuronal TLR3, TLR7 and TLR8 with nucleic acids negatively modulates neurite outgrowth and alters synapse formation in a cell-autonomous manner. It consequently influences neural connectivity and brain function and leads to deficits related to neuropsychiatric disorders. Importantly, neuronal TLR activation does not simply duplicate the downstream signal pathways and effectors of classical innate immune responses. The differences in spatial and temporal expression of TLRs and their ligands likely account for the diverse signaling pathways of neuronal TLRs. In conclusion, the accumulated evidence strengthens the idea that the innate immune system of neurons serves as an alarm system that responds to exogenous pathogens as well as intrinsic danger signals and fine-tune developmental processes of neurons.

Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.

BACKGROUND: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development. METHODS: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals. RESULTS: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer. CONCLUSION: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.

Estimated glomerular filtration rate and arterial stiffness in Japanese population: a secondary analysis based on a cross-sectional study.

BACKGROUND: Evidence regarding the relationship between estimated glomerular filtration rate (eGFR) and arterial stiffness is limited, and the data analysis is not sufficient to clarify the true relationship between the two. We aimed to investigate the relationship between eGFR and brachial-ankle pulse wave velocity (baPWV) in Japanese. METHODS: The present study was a cross-sectional study. Nine hundred twelve Japanese men and women, aging 24-84 years old, received a health medical check-up program including the results from baPWV inspection and various standardized questionnaires in a health examination center in Japan. The main outcome measures included eGFR, baPWV, fatty liver and postmenopausal status. Abdominal ultrasonography was used to diagnose fatty liver. Postmenopausal state was defined as beginning 1 year after the cessation of menses. RESULTS: The average age of the 912 selected participants was 51.5 ± 9.6 years old, and about 57.6% of them were male. The participants' eGFR distribution was median 69.29 (min 39, max 122.28). The results of multivariate linear regression showed eGFR was not independently associated with baPWV after adjusting potential confounders (ß = - 1.11, 95%CI -2.25 to 0.03), this is inconsistent with the result of eGFR (quartile) as a categorical variable (p for trend was 0.038). A non-linear relationship was detected between eGFR and baPWV, whose point was 77.05. The effect sizes and the confidence intervals of the left and right sides of inflection point were - 2.80 (- 4.41 to - 1.19) and 1.84 (- 0.50, 4.17), respectively. Subgroup analysis showed, the change in the elderly population is more pronounced (P for interaction = 0.018; - 2.83 with ≤60 year vs - 6.12 with > 60 year). The same trend was also seen in hypertensive people (P for interaction = 0.018; - 4.55 with hypertension vs - 0.82 with non-hypertension). CONCLUSION: The relationship between eGFR and baPWV is non-linear. eGFR was negatively related to baPWV when eGFR is less than 77.05.

Association between lipoproteins and telomere length in US adults: data from the NHANES 1999-2002.

BACKGROUND: Evidence regarding the correlation between lipoproteins and telomere length in US adults is limited. We aimed to investigate whether lipoproteins was associated with telomere length using US National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 6468 selected participants were identified in the NHANES Data Base (1999-2002). The independent and dependent variables were lipoproteins and telomere length, respectively. The covariates included demographic data, dietary data, physical examination data, and comorbidities. RESULTS: In fully-adjusted model, we found that 0.1 differences of telomere length were positively associated with HDL-C [0.19 (95% CI 0.07, 0.31)], while the associations between LDL-C [0.19 (95% CI -0.27, 0.65)], TG [- 1.00 (95% CI -2.09, 0.07) and telomere length were not detected. By nonlinearity test, only the relationship between HDL-C and telomere length was nonlinear. The inflection point we got was 1.25. On the left side of the inflection point (telomere length ≤ 1.25), a difference in 0.1 of telomere length was associated with 0.50 difference in HDL-C. CONCLUSION: After adjusting for demographic data, dietary data, physical examination data, and comorbidities, telomere length is not associated with LDL-C and TG, but is positively associated with HDL-C when telomere length is less than 1.25.

Tlr7 deletion alters expression profiles of genes related to neural function and regulates mouse behaviors and contextual memory.

The neuronal innate immune system recognizes endogenous danger signals and regulates neuronal development and function. Toll-like receptor 7 (TLR7), one of the TLRs that trigger innate immune responses in neurons, controls neuronal morphology. To further assess the function of TLR7 in the brain, we applied next generation sequencing to investigate the effect of Tlr7 deletion on gene expression in hippocampal and cortical mixed cultures and on mouse behaviors. Since previous in vivo study suggested that TLR7 is more critical for neuronal morphology at earlier developmental stages, we analyzed two time-points (4 and 18 DIV) to represent young and mature neurons, respectively. At 4 DIV, Tlr7 KO neurons exhibited reduced expression of genes involved in neuronal development, synaptic organization and activity and behaviors. Some of these Tlr7-regulated genes are also associated with multiple neurological and neuropsychiatric diseases. TLR7-regulated transcriptomic profiles differed at 18 DIV. Apart from neuronal genes, genes related to glial cell development and differentiation became sensitive to Tlr7 deletion at 18 DIV. Moreover, Tlr7 KO mice exhibited altered behaviors in terms of anxiety, aggression, olfaction and contextual fear memory. Electrophysiological analysis further showed an impairment of long-term potentiation in Tlr7 KO hippocampus. Taken together, these results indicate that TLR7 regulates neural development and brain function, even in the absence of infectious or pathogenic molecules. Our findings strengthen evidence for the role of the neuronal innate immune system in fine-tuning neuronal morphology and activity and implicate it in neuropsychiatric disorders.

Deletion of the Inflammasome Sensor Aim2 Mitigates Aß Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model.

OBJECTIVE: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. METHODS: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice. RESULTS: We found that Aim2 knockout mitigates Aß deposition in the cerebral cortex and hippocampus of 5XFAD mice. The activation of microglial cells is also reduced in Aim2-/-;5XFAD brains compared with 5XFAD brains. However, Aim2 knockout does not improve memory and anxiety phenotypes of 5XFAD mice in an open field, cued Y-maze, or Barnes maze. Compared with 5XFAD mice, Il-1 expression levels are not reduced in Aim2-/-;5XFAD mice. Unexpectedly, Il-6 and Il-18 expression levels in 5XFAD brains were further increased when Aim2 was deleted. Thus, inflammatory cytokine expression in 5XFAD brains is upregulated by Aim2 deletion through an unknown mechanism. CONCLUSION: Although Aim2 knockout mitigates Aß deposition and microglial activation, Aim2 deletion does not have a beneficial effect on the spatial memory or cytokine expression of 5XFAD mice. Our findings suggest that Aß aggregation and microglial activation may not always be correlated with the expression of inflammatory cytokines or cognitive function of 5XFAD mice. Our study also implies that different inflammasomes likely perform distinct roles in different physiological and/or pathological events.

[Value of combined measurement of intestinal fatty acid-binding protein and fecal calprotectin in diagnosis of necrotizing enterocolitis in full-term neonates].

OBJECTIVE: To study the value of combined measurement of intestinal fatty acid-binding protein (I-FABP) and fecal calprotectin (FC) in the diagnosis of necrotizing enterocolitis (NEC) in full-term neonates. METHODS: A total of 36 full-term neonates with NEC (case group) and 39 neonates without digestive system diseases (control group) were enrolled as study subjects. ELISA was used to measure the serum I-FABP level and fecal FC level, and the clinical value of I-FABP combined with FC in the diagnosis of NEC was evaluated. RESULTS: The case group had significantly higher I-FABP and FC levels than the control group (P<0.05). In the case group, serum I-FABP level was positively correlated with fecal FC level (r=0.71, P<0.05). In the diagnosis of NEC, I-FABP alone, FC alone, and I-FABP/FC combination had sensitivities of 83.3%, 81.5%, and 79.5%, specificities of 72.5%, 75.8%, and 86.3%, and areas under the ROC curve (AUCs) of 0.82, 0.81, and 0.88. The combined measurement showed significantly higher specificity and AUC than single measurement (P<0.05). CONCLUSIONS: Children with NEC have significant increases in I-FABP and FC levels, and there is a correlation between them. Combined measurement of I-FABP and FC can increase the specificity of the diagnosis of NEC.

[Investigation of the arsenic levels in ecosystem aspect in water type of endemic arsenicosis area in Datong City].

OBJECTIVE: To investigate the arsenic levels in endemic arsenism in Datong City, Shanxi Province. METHODS: A total of 85 inhabitants from one village in endemic arsenism area in Datong City, Shanxi Province were collected as research subjects. The People's Republic of China health industry standard for endemic arsenism was used to identify and diagnosis the patients. Daily drinking water and soil were collected and detected by atomic fluorescence spectrometry. The content of vegetables were detected by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: In the study, 85 samples were collected. Arsenic concentration in the daily drinking water were 14.41 - 90.34 µg/L, and the median value was 43.88 µg/L. The arsenic concentration of vegetables were 0.001 - 0.771 mg/kg, and 43.04% of samples, were higher than the maximal permissible limit of As in food. The results that the arsenic concentration of vegetables constant changes in the leaf vegetables > tubers > fruit vegetables. The health risk of intaking arsenic pollution in vegetables up to 71.77%. The arsenic levels in village of four directions were not exceeded the Chinese standards. CONCLUSIONS: Arsenic concentration in drinking water and vegetables are high in waterborn endemic arsenicosis area of Shanxi province. Arsenic in drinking water has been considered as a primary cause of arsenism, but direct intake of arsenic from vegetables can not be ignored.

TLR7 negatively regulates dendrite outgrowth through the Myd88-c-Fos-IL-6 pathway.

Toll-like receptors (TLRs) recognize both pathogen- and danger-associated molecular patterns and induce innate immune responses. Some TLRs are expressed in neurons and regulate neurodevelopment and neurodegeneration. However, the downstream signaling pathways and effectors for TLRs in neurons are still controversial. In this report, we provide evidence that TLR7 negatively regulates dendrite growth through the canonical myeloid differentiation primary response gene 88 (Myd88)-c-Fos-interleukin (IL)-6 pathway. Although both TLR7 and TLR8 recognize single-stranded RNA (ssRNA), the results of quantitative reverse transcription-PCR suggested that TLR7 is the major TLR recognizing ssRNA in brains. In both in vitro cultures and in utero electroporation experiments, manipulation of TLR7 expression levels was sufficient to alter neuronal morphology, indicating the presence of intrinsic TLR7 ligands. Besides, the RNase A treatment that removed ssRNA in cultures promoted dendrite growth. We also found that the addition of ssRNA and synthetic TLR7 agonists CL075 and loxoribine, but not R837 (imiquimod), to cultured neurons specifically restricted dendrite growth via TLR7. These results all suggest that TLR7 negatively regulates neuronal differentiation. In cultured neurons, TLR7 activation induced IL-6 and TNF-α expression through Myd88. Using Myd88-, IL-6-, and TNF-α-deficient neurons, we then demonstrated the essential roles of Myd88 and IL-6, but not TNF-α, in the TLR7 pathway to restrict dendrite growth. In addition to neuronal morphology, TLR7 knockout also affects mouse behaviors, because young mutant mice ∼2 weeks of age exhibited noticeably lower exploratory activity in an open field. In conclusion, our study suggests that TLR7 negatively regulates dendrite growth and influences cognition in mice.

Prognostic value of secreted phosphoprotein-1 in pleural effusion associated with non-small cell lung cancer.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication of advanced lung cancer. Research has shown that secreted phosphoprotein-1 (SPP1) is essential in MPE associated with lung cancer. This retrospective study was performed to evaluate the prognostic significance of SPP1 in the MPE of patients with non-small cell lung cancer (NSCLC). METHODS: MPE specimens were obtained from 85 NSCLC patients (study group), and pleural effusion specimens were obtained from 24 patients with benign lung disease (control group). Specimens were tested for SPP1 using enzyme-linked immunosorbent assay (ELISA). Based on the cutoff value of receiver operating characteristic (ROC) curve analysis, the study patients were divided into a high-SPP1-expression subgroup and a low-expression subgroup. The primary and secondary endpoints of this study were progression-free survival (PFS) and overall survival (OS). RESULTS: The SPP1 levels of the study group were significantly higher compared to those of the controls (Mann-Whitney U test, P = 0.017). The number of extrapulmonary metastases was significantly higher in the high-SPP1-expressing patients than in the low-expressing patients (P = 0.03). Kaplan-Meier survival analysis showed that SPP1 levels were negatively associated with OS and PFS in both subgroups of study patients (P = 0.026; P = 0.039, respectively). Cox regression analysis showed that SPP1 was an independent prognostic factor in patients with NSCLC (HR = 1.832, 95% confidence interval: 1.003-3.345; P = 0.049). CONCLUSION: SPP1 in pleural effusion can be used for the auxiliary diagnosis of MPE and used to determine the prognosis of patients with NSCLC.

[Clinical significance of serum intestinal fatty acid-binding protein in full-term infants with necrotizing enterocolitis].

OBJECTIVE: To evaluate the clinical value of intestinal fatty acid-binding protein (I-FABP) in full-term newborn infants with necrotizing enterocolitis (NEC). METHODS: Forty-one full-term infants with a confirmed diagnosis of NEC from February 2012 to January 2014 were recruited as case group (stage I: 24 cases; stage II-III: 17 cases). Sixty-two children diagnosed with non-digestive diseases in the same period were recruited as the control group. Serum levels of I-FABP and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay. The diagnostic value of I-FABP for NEC was assessed using the receiver operating characteristic (ROC) curve. RESULTS: Stage I and stage II-III cases in the case group had significantly higher serum I-FABP levels than the control group (P<0.05), and stage II-III cases had significantly higher serum I-FABP levels than stage I cases (P<0.05). The area under the ROC curve for serum I-FABP was 0.85 (95% CI: 0.78-0.92), with the optimal cut-off point of 2.25 ng/mL. Under this cut-off point, the sensitivity and specificity were 80.49% and 70.19%, respectively. There was no significant difference in serum CRP level between the case and control groups (P>0.05). CONCLUSIONS: In newborn infants with NEC, serum I-FABP level increases significantly in stage I , and it is correlated with the disease severity. Therefore, serum I-FABP can be used as a biomarker for the diagnosis of NEC.

Research progress on the mechanism of common inflammatory pathways in the pathogenesis and development of lymphoma.

In recent years, the incidence and mortality rates of lymphoma have gradually increased worldwide. Tumorigenesis and drug resistance are closely related to intracellular inflammatory pathways in lymphoma. Therefore, understanding the biological role of inflammatory pathways and their abnormal activation in relation to the development of lymphoma and their selective modulation may open new avenues for targeted therapy of lymphoma. The biological functions of inflammatory pathways are extensive, and they are central hubs for regulating inflammatory responses, immune responses, and the tumour immune microenvironment. However, limited studies have investigated the role of inflammatory pathways in lymphoma development. This review summarizes the relationship between abnormal activation of common inflammatory pathways and lymphoma development to identify precise and efficient targeted therapeutic options for patients with advanced, drug-resistant lymphoma.

Inflammatory pathways directly or indirectly regulate the TME and are closely related to the development of lymphoma.This review was conducted to elucidate the connection between inflammatory pathways and the tumorigenesis and drug resistance of several common lymphomas.Overall, targeting abnormally activated molecules upstream and downstream of lymphoma inflammatory pathways in the future is expected to be a new target for lymphoma treatment.

Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient: A case report.

BACKGROUND: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH. CASE SUMMARY: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 µg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 µg/L. The patient's clinical symptoms demonstrated a notable improvement. CONCLUSION: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

Sesquiterpenoids from aged Artemisia argyi and their 3D-QSAR for anti-HBV activity.

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine.

Tsaokoflavanols A1-J1: Flavanol-fatty alcohol hybrids with HPL inhibitory activity from Amomum tsao-ko.

Ten previously undescribed compounds were isolated from the fruits of Amomum tsao-ko (Zingiberaceae), including nine undescribed flavanol-fatty alcohol hybrids (1-6, 10-11, 13), and a flavanol-monoterpenoid hybrid (14), along with seven known flavanol hybrids (7-9, 12, 15-17). The structures of these compounds were determined using various analyses, such as HRESIMS, 1D/2D NMR, and ECD calculations. In terms of biological activity, compounds 1, 2, 5, and 6 exhibited inhibitions of human pancreatic lipase (HPL), with IC50 values ranging from 0.017 to 0.193 mM. Some of these values were found to be stronger than that of the positive control, orlistat (IC50, 0.067 mM). Molecular docking studies were also conducted to investigate the interactions between these compounds and HPL. The docking simulations revealed the importance of the orientation of the 3,4-dihydroxyphenyl in binding with HPL. Additionally, compound 9 demonstrated cytotoxicity against HepG2, with a CC50 value of 14.96 ± 0.62 µM as determined by the MTT assay. Flow cytometry analysis indicated that compound 9 induced apoptosis in HepG2 cells. Western blot results showed an up-regulation of apoptosis-related proteins, such as p53 protein, Bax and Caspase-3 proteins, while the expression of Bcl-2 protein was down-regulated.

BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause.

BACKGROUND: The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. RESULTS: Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007). CONCLUSIONS: BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs.

Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions.

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic.