Effects of 2,3',4,4',5-pentachlorobiphenyl exposure during pregnancy on DNA methylation in the testis of offspring in the mouse.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants, and the widespread use of PCBs has had adverse effects on human and animal health. This study experiment explored the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on the mammalian reproductive system. PCB118 was administered to pregnant mice from 7.5 to 12.5 days of gestation; F1 mice were obtained and the reproductive system of F1 male mice was examined. PCB118 damaged the reproductive system in male F1 mice, as evidenced by negative effects on the testicular organ coefficient (testes weight/bodyweight), a decrease in the diameter of seminiferous tubules and a significant reduction in the anogenital distance in 35-day-old F1 mice. In addition, methylation levels of genomic DNA were reduced, with reductions in the expression of the DNA methyltransferases DNMT1, DNMT3A and DNMT3B, as well as that of the epigenetic regulatory factor ubiquitin like with PHD and ring finger domains 1 (Uhrf1). Together, the results of this study provide compelling evidence that exposure of pregnant mice to PCB118 during primordial germ cell migration in the fetus affects the reproductive system of the offspring and decreases global methylation levels in the testis.

Semi-Rigid Thoracoscopic Punch Biopsy Using a Hybrid Knife with a High-Pressure Water Jet for the Diagnosis of Pleural Effusions.

Semi-rigid thoracoscopy is an important technique in the definitive diagnosis of pleural diseases with high diagnostic sensitivity and specificity. Obtaining adequate samples from thickened pleura is the most important limitation of semi-rigid thoracoscopy with a standard flexible forceps (SFF) compared with rigid thoracoscopy, especially in patients with mesothelioma or benign fibrothorax. Developing a convenient, efficient and safe biopsy technique to obtain sufficient samples from such patients is a key topic in semi-rigid thoracoscopy. The hybrid knife (HK) is an innovative design fusing high-pressure water injection and a conventional diathermic knife that can allow for the safe resection of a larger lesion during gastrointestinal endoscopic dissection. Here, we describe 3 patients with unexplained pleural effusion who underwent pleural biopsy using an HK to investigate the potential use of the HK as a new pleural biopsy device in semi-rigid thoracoscopy when pleural lesions are difficult to biopsy using an SFF. The biopsies were obtained successfully by HK, and the diagnosis followed. The sizes of the biopsies collected by HK are larger than those collected by SFF. No complications were observed. Electrocautery biopsy using an HK during semi-rigid thoracoscopy has great potential for diagnosing consistent abnormal pleuras, which are difficult to biopsy with an SFF.

The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy.

BACKGROUND: Circulating microRNA 130b has been closely associated with multiple diseases in humans such as cancer, obesity and diabetes mellitus. This study evaluates the correlation between serum miR-130b and the severity of diabetic nephropathy evaluated by measurement of albuminuria. METHODS: Three hundred twenty-seven patients with type 2 diabetes mellitus (T2DM) were divided into three groups: normoalbuminuria group [diabetes mellitus, urinary albumin to creatinine ratio (UACR) < 30 mg/g, n = 137], microalbuminuria group (DN1, UACR 30-300 mg/g, n = 122) and macroalbuminuria group (DN2, UACR > 300 mg/g, n = 68). The levels of serum miR-130b were validated by real-time polymerase chain reaction. Serum transforming growth factor ß1 (TGF-ß1), hypoxia inducible factor 1α (HIF-1α) and fibronectin were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with control, serum miR-130b levels were significantly decreased in T2DM patients and further decreased in the patients of diabetes mellitus, DN1 and DN2 groups (p < 0.001). Furthermore, age-adjusted and sex-adjusted regression analyses showed that decreased level of serum miR-130b, increased levels of glycated haemoglobin (HbA1c ), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein (LDL), serum creatinine, blood urea nitrogen (BUN), TGF-ß1, HIF-1α and fibronectin were significantly correlated with UACR (p < 0.05). In addition, serum miR-130b levels were inversely correlated with HbA1c , HOMA-IR, TG, LDL, BUN, TGF-ß1, HIF-1α and FN (p < 0.05). CONCLUSION: Our findings suggest that serum miR-130b may be a new biomarker for the early diagnosis of DN in T2DM. Circulating miR-130b may possibly be involved in the pathological mechanism of DN, such as lipid metabolic disorders, oxidative stress, extracellular matrix deposition and renal fibrosis.

The Relationship between Serum Osteocalcin Concentration and Glucose and Lipid Metabolism in Patients with Type 2 Diabetes Mellitus ­ The Role of Osteocalcin in Energy Metabolism.

BACKGROUND: Recent animal studies have found that the osteocalcin secreted by osteoblasts could participate in glucose and lipid metabolism. Our study aimed to investigate the relationship between serum osteocalcin concentration and glucose and lipid metabolism in patients with type 2 diabetes mellitus. METHODS: 985 patients with type 2 diabetes were divided into the male group (n = 495) and the postmenopausal female group (n = 490). The average ages were 54.42 ± 10.535 and 64.93 ± 9.277, respectively. We collected the parameters of age, duration, fasting plasma glucose, HbA1c, fasting insulin, fasting C peptide, blood lipid, 25 (OH) VD3, parathyroid hormone (PTH), Alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), ß-C-terminal telopeptide of type I collagen (ß-CTx), osteocalcin, HOMA-IR, HOMA-ß, body mass index (BMI), and waist-to-hip ratio (WHR). The relationship of osteocalcin and these parameters were analyzed by Pearson/Spearman correlation analysis and stepwise multiple regression analysis. RESULTS: Osteocalcin was negatively correlated with HbA1c (p < 0.05) and it was also an independent relevant factor affecting HbA1c in both groups. Osteocalcin was positively correlated with HOMA-ß and it was an independent relevant factor affecting HOMA-ß in male group (p < 0.01). CONCLUSIONS: These findings indicate the association between serum osteocalcin and glucose metabolism and beta cell function. No relationship was found between osteocalcin and insulin resistance and lipid metabolism in type 2 diabetes.

Evaluation of drug interactions of Saposhnikoviae Radix and its major components with astragaloside IV and paeoniflorin using in vitro and in vivo experiments.

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.

The First Report of Tritrichomonas Foetus and Tetratrichomonas Buttreyi in Raccoon Dogs (Nyctereutes Procyonoides) in China.

BACKGROUND: In recent years, the trichomonosis in raccoon dogs in China had occurred frequently. Pentatrichomonas hominis had been described in raccoon dogs in China in some previous studies. PURPOSE TO REVEAL: whether raccoon dogs can be infected by other trichomonad species besides P. hominis, and clarify the prevalence and species distribution of trichomonad in raccoon dogs. METHODS: Herein, the 389 fecal samples were collected from farm-raised raccoon dogs in Hebei Province, all the samples were detected using the microscopic examination and several fecal samples containing trichomonad-like organisms were processed, cultured, stained, and photographed. Meanwhile, all the samples were screened by the species-specific nested PCR based on the small subunit rRNA (SSU rRNA) gene of P. hominis,Tritrichomonas foetus and Tetratrichomonas buttreyi, respectively, and all positive secondary PCR amplications obtained in this study were sequenced, aligned and analysed. RESULTS: 62 fecal samples (15.9%,62/389) were trichomonad-positive under light microscopy, and the trichomonad-like cells were clearly observed in the culture contents. The PCR results showed that 100 samples were trichomonad-positive, including 45 P. hominis-positive samples (11.6%,45/389), 32 T. foetus-positive samples (8.2%,32/389), and 33 T. buttreyi-positive samples (8.5%,33/389), respectively. Double mixed infections were observed in 10 samples. The prevalence of T. foetus and P. hominis were both significantly higher in raccoon dogs with diarrhea (13.9%, and 25.0%) than that in raccoon dogs without diarrhea (7.6%, and 9.3%) (p < 0.05).All samples confirmed as trichomonad-positive under microscopy were also found to be trichomonad-positive by PCR analysis. The sequencing and phylogenetic analysis demonstrated the sequences obtained in this study belonged to P. hominis, T. foetus and T. buttreyi SSU rRNA, respectively. Among them, the T. buttreyi SSU rRNA sequences obtained in this study harbored the new sequence polymorphisms. Based on preliminary morphological and molecular analyses, raccoon dogs are considered as the new host of T. foetus and T. buttreyi. CONCLUSION: This is the first report about the identifcation and prevalence of T. foetus and T. buttreyi in raccoon dogs in China, and the results increase our knowledge about the host range and prevalence of trichomonad species.

Regulation of cigarette smoke-induced toll-like receptor 4 expression by peroxisome proliferator-activated receptor-gamma agonists in bronchial epithelial cells.

BACKGROUND AND OBJECTIVE: This study was designed to determine the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) on airway inflammatory response to cigarette smoke (CS) exposure. METHODS: For the in vivo experiments, 50 male Wistar rats were randomly assigned to one of four groups and were exposed to CS and pretreatment with a PPARγ agonist, rosiglitazone or a vehicle (saline). PPARγ antagonist bisphenol A diglycidyl ether (BADGE) or saline was administered before rosiglitazone treatment. Leukotriene B4 (LTB4) and interleukin-8 (IL-8) were measured by enzyme-linked immunosorbent assay. PPARγ and toll-like receptor 4 (TLR4) expression levels were assessed by immunohistochemistry and real-time polymerase chain reaction. For the in vitro experiments, human bronchial epithelial cells were stimulated with CS or phosphate buffer saline, pretreated with PPARγ agonist rosiglitazone or 15-deoxy-(Δ12,14)-PG J2 before CS exposure. BADGE was administered prior to the agonist treatment. PPARγ, TLR4 and inhibitor of κB (IκBα) expression levels were assessed by Western bot. RESULTS: CS exposure decreased PPARγ expression, as well as increased IL-8, LTB4 and TLR4 expression levels in bronchial epithelial cells in vivo and in vitro. Moreover, PPARγ ligands counteracted CS-induced airway inflammation by reducing IL-8 and LTB4 expression levels that are associated with TLR4 and nuclear factor-kappa B (NF-κB). CONCLUSION: CS exposure increased the pro-inflammatory activity of bronchial epithelial cells by affecting PPARγ expression. Moreover, PPARγ may play a significant role as a modulator of the TLR4-dependent inflammatory pathway through NF-κB in bronchial epithelial cells.

2,3',4,4',5-Pentachlorobiphenyl induces mitochondria-dependent apoptosis mediated by AhR/Cyp1a1 in mouse germ cells.

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 µg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.

Clinical impact of liquid-based cytology test on diagnostic yields from transbronchial needle aspiration.

BACKGROUND AND OBJECTIVE: Transbronchial needle aspiration (TBNA) is a well-established diagnostic method that is underutilized due to the relatively high percentage of non-diagnostic samples and low success rates. This study was designed to evaluate the impact of liquid-based cytology test (LBC) on the diagnostic yield from TBNA. METHODS: Ninety-seven consecutive patients who underwent TBNA due to significant mediastinal adenopathy were enrolled in the study. Each target site was aspirated four times, with the first and third aspirates being prepared for LBC and the second and fourth aspirates being reserved for conventional pick-and-smear (CPS) cytology. RESULTS: Paired aspirates were obtained from 114 target sites, giving a total of 228 test samples from 97 consecutive patients. The overall diagnostic sensitivity of TBNA was 63.6% (56/88). The yields from small cell lung cancers were better than those from non-small cell lung cancers (P < 0.05), and TBNA of subcarinal nodes provided better diagnostic yields (P < 0.05). Nodal diameters > 20 mm on computed tomography were also associated with better yields than nodes with diameters of 10-20 mm (P = 0.001). The diagnostic sensitivity of TBNA was similar for each processing method-59.8% (61/102) for LBC and 64.7% (65/102) for CPS. CONCLUSIONS: LBC was not inferior to CPS with respect to diagnostic yields from TBNA, and enabled efficient pathological evaluation.

CT Attenuation and Cross-Sectional Area of the Pectoralis Are Associated With Clinical Characteristics in Chronic Obstructive Pulmonary Disease Patients.

Purpose: Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). Computed tomography (CT) could serve as a method for muscle assessment due to its ability to measure both muscle quantity (e.g., cross-sectional muscle area) and muscle quality (e.g., muscle attenuation). Our study aimed to compare the differences in CT-derived pectoralis muscle cross-sectional area (PMA) and pectoralis muscle attenuation (PMT) between COPD patients and healthy controls and explore the association between PMA and PMT measurements and clinical characteristics in patients with COPD. Methods: A total of 252 participants included in our analysis consisted of 80 healthy controls and 172 patients with COPD. PMA and PMT were measured from a single axial slice of the CT scan above the aortic arch. Linear regression analysis was used to determine the correlation between PMA and PMT measurements and clinical characteristics in patients with COPD. Associations were adjusted for age, sex, BMI, FEV1%pred, smoking pack-years, current smoking status, emphysema percentage, and total airway count (TAC) of the right upper lobe apical bronchus (RB1). Results: PMA and PMT were lower in COPD patients, especially those with acute exacerbation, than in healthy controls. PMA and PMT were significantly associated with the severity of emphysema and the TAC of RB1 (p < 0.05). Patients with stable COPD, who had lower PMA and lower PMT, had significantly worse pulmonary function, poorer exercise tolerance, decreased quality of life, and worse dyspnea scores. In addition, patients with acute COPD exacerbation, who had lower PMA and lower PMT, had a higher risk of respiratory failure on admission. Conclusion: CT-derived measurements of the pectoralis muscle may be helpful in detecting declines in muscle quantity and quality and predicting disease severity in patients with COPD.

Surface charge switchable nano-micelle for pH/redox-triggered and endosomal escape mediated co-delivery of doxorubicin and paclitaxel in treatment of lung adenocarcinoma.

Recently, the stimulus-sensitive drug co-delivery system has gained increasing attentions in the clinic and exhibits improved efficiency rather than the mono-chemotherapy in anti-tumor therapy. Herein, the smart charge switchable nano-micelles (NMs) were fabricated for the endosomal escape mediated co-delivery of doxorubicin (DOX) and paclitaxel (PTX) in treatment of lung adenocarcinoma. The disulfide bonds were facilitated as the linker of the polymer backbone to achieve the redox-sensitive degradation by high intracellular GSH, and acid-liable DMMA was grafted onto DOX molecules for pH-triggered drug release under acidic tumoral microenvironment. Folic acid (FA) was utilized as targeting molecule for facilitating entry of the as prepared NMs into cancer cells. Remarkably, the as fabricated NMs exhibited surface charge-switch from negative to positive during transmitting from physiological pH to the tumor extracellular pH, which can improve the cellular internalization towards cancer cell. Subsequently, the "proton-sponge" effect mediated endosome escape of the NMs was facilitated in the acidic endo/lysosome environment. By the cell assay, the NMs possessed good biocompatibility, excellent cellular uptake, and improved inhibition rate against cancer cell. Moreover, the co-delivery of DOX/PTX exhibited synergistic and enhanced solid tumor inhibition efficiency comparing to mono-chemotherapy in A-549 tumor bearing mice model. Based on above experimental results, the as prepared drug co-delivery system showed promising biosafety and potentials for efficient lung adenocarcinoma treatment in clinic.

Sublethal and Transgenerational Toxicities of Chlorfenapyr on Biological Traits and Enzyme Activities of Paracoccus marginatus (Hemiptera: Pseudococcidae).

Papaya mealybug, Paracoccus marginatus Williams and Granara de Willink (Hemiptera: Pseudococcidae), is an economically important, invasive insect that is now distributed worldwide. Chlorfenapyr has been demonstrated to have a significant control effect on P. marginatus. In order to evaluate the sublethal and transgenerational effects of chlorfenapyr on P. marginatus, the life table data of three consecutive generations were collected and analyzed by the age stage, two-sex life table method, and the enzyme activities were assayed using a spectrophotometer. The results showed that exposure to the insecticide had significant effects on the biological traits of subsequent generations of P. marginatus, and a higher intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and a shorter mean generation time (T) were observed in the chlorfenapyr-treated F1 mealybugs. Enzyme activity assays showed that chlorfenapyr significantly inhibited the activities of catalase (CAT) and peroxidase (POD) while activating the activities of superoxide dismutase (SOD), which suggested that SOD, CAT, and POD may play an important role in the self-defense of P. marginatus against chlorfenapyr. These results conclusively demonstrated that exposure of P. marginatus to sublethal concentrations of chlorfenapyr induced hormetic effects on the F1 generation while having negative effects on the F0 and F3 generations.

The Novel Regulatory Role of the lncRNA-miRNA-mRNA Axis in Chronic Inflammatory Airway Diseases.

Chronic inflammatory airway diseases, characterized by airway inflammation and airway remodelling, are increasing as a cause of morbidity and mortality for all age groups and races across the world. The underlying molecular mechanisms involved in chronic inflammatory airway diseases have not been fully explored. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have recently attracted much attention for their roles in the regulation of a variety of biological processes. A number of studies have confirmed that both lncRNAs and miRNAs can regulate the initiation and progression of chronic airway diseases by targeting mRNAs and regulating different cellular processes, such as proliferation, apoptosis, inflammation, migration, and epithelial-mesenchymal transition (EMT). Recently, accumulative evidence has shown that the novel regulatory mechanism underlying the interaction among lncRNAs, miRNAs and messenger RNAs (mRNAs) plays a critical role in the pathophysiological processes of chronic inflammatory airway diseases. In this review, we comprehensively summarized the regulatory roles of the lncRNA-miRNA-mRNA network in different cell types and their potential roles as biomarkers, indicators of comorbidities or therapeutic targets for chronic inflammatory airway diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma.

Zwitterionic meso-silica/polypeptide hybrid nanoparticles for efficient azithromycin delivery and photodynamic therapy for synergistic treatment of drug-resistant bacterial infection.

The treatment of drug-resistant bacterial infections attributed to the overuse of antibiotics still remains a serious challenge globally. Herein, zwitterionic charge switchable meso-silica/polypeptide hybrid nanoparticles (MSPNs) were prepared for the synergistic chemo-photodynamic therapy in the treatment of drug-resistant bacterial infections. Subsequently, azithromycin (AZT) and methylene blue (MB) were loaded in the MSPNs to form the combined chemo-photodynamic therapeutic nanoparticles (MSPNs-AZT/MB) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, the as-prepared MSPNs-AZT/MB exhibited a negative surface charge of -5.2 mV at physiological pH while switching into positive surface charge of 24.7 mv in an acidic environment, leading to enhanced binding with bacterial surface. The lipase-triggered AZT release up to 77.9 % was achieved, and the loaded MB demonstrated efficient singlet oxygen (1O2) generation for photodynamic therapy. The in vitro experimental results displayed an excellent antibacterial effect against MRSA in both planktonic and biofilm phenotypes. Additionally, the as-prepared MSPNs-AZT/MB exhibited synergistic and enhanced antibacterial infection effect up to 94 % comparing to monotherapy in a mice model. Considering the above advantages, the as-prepared combined chemo-photodynamic therapeutic nanoparticles showed promising biocompatibility and clinical potential for the efficient therapy of drug-resistant bacteria.

[The effect of fasudil via Rho/ROCK signaling pathway on the inflammation and fibrosis in human mesangial cells in high glucose medium].

OBJECTIVE: To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. METHODS: Synchronized HMCs were divided into following groups: (1) Normal glucose control group (NG, 5.5 mmol/L glucose); (2) High glucose group (HG, 30 mmol/L glucose); (3) Mannitol group (Man, 5.5 mmol/L glucose + 24.5 mmol/L mannitol); (4) High glucose + fasudil group (HG + F, the concentrations of fasudil were 25, 50 and 100 µmol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK-I, connective tissue growth factor (CTGF)mRNA with real-time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin (FN), CTGF, TNFα in the supernatant. RESULTS: (1) RhoA, ROCK-I and CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time-dependence. Besides, there was no statistic significance by comparing Man and NG. (2)Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK-I, CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFα protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFα protein secretion was significantly reduced compared with HG. CONCLUSION: Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy.

[Effects of inhibiting RhoA by Stealth RNA on high glucose-induced RhoA/ROCK signaling pathway in human mesangial cells].

OBJECTIVE: To observe the effect of small interference RNA (Stealth RNAiTM siRNA) of RhoA on the inflammatory response and fibrosis in human mesangial cell (HMC) and explore the role of RhoA/ROCK signaling pathway in the process of diabetic nephropathy. METHODS: Synchronized HMC were divided into several groups. Lipofectamine(TM)2000 was employed to transfect RhoA-siRNA and RhoA-negative siRNA into the above cells. RhoA-siRNA could inhibit the expression of RhoA. The expressions of RhoA, ROCK-I, fibronectin (FN), connective tissue growth factor (CTGF) and tumor necrosis factor-alpha (TNF-α) were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA (enzyme-linked immunosorbent assay). RESULTS: (1) The expressions of RhoA, ROCK-I and CTGF mRNA were inhibited by RhoA siRNA transfection in high glucose-induced HMC. The expression of each mRNA was reduced 26% - 60% as compared with the high glucose-induced group (P < 0.05); (2) After RhoA siRNA transfection and culturing with high glucose for 48 h, FN, the secretions of CTGF and TNF-α significantly declined [FN: (1.99 ± 0.04) mg/L vs. (4.31 ± 0.13) mg/L, CTGF:(4.98 ± 0.17) mg/L vs. (6.06 ± 0.09) mg/L; TNF-α: (61.17 ± 2.59) ng/L vs.(91.76 ± 2.27) ng/L, all P < 0.05]. The levels of FN and CTGF almost decreased to those of normal glucose-induced HMC. CONCLUSION: The levels of FN, CTGF and TNF-α in high glucose-induced HMC may be lowered by inhibiting RhoA through RNA interference and reducing the accumulation of extracellular matrix, glomerular fibrosis and inflammation. Thus it provides a new intervention target for the prevention of diabetic nephropathy.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction.

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1ß, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1ß, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

Disulfide Cross-Linked Poly(Methacrylic Acid) Iron Oxide Nanoparticles for Efficiently Selective Adsorption of Pb(II) from Aqueous Solutions.

The efficient selectivity of heavy metal ions from wastewater is still challenging but gains great public attention in water treatment on a world scale. In this study, the novel disulfide cross-linked poly(methacrylic acid) iron oxide (Fe3O4@S-S/PMAA) nanoparticles with selective adsorption, improved adsorption capability, and economic reusability were designed and prepared for selective adsorption of Pb(II) ions in aqueous solution. In this study, nuclear magnetic resonance, dynamic light scattering, scanning electron microscopy, X-ray diffraction, vibrating sample magnetometry, and thermogravimetric analysis were utilized to study the chemophysical properties of Fe3O4@S-S/PMAA. The effect of different factors on adsorption properties of the Fe3O4@S-S/PMAA nanoparticles for Co(II) and Pb(II) ions in aqueous solution was explored by batch adsorption experiments. For adsorption mechanism investigation, the adsorption of Fe3O4@S-S/PMAA for Co(II) and Pb(II) ions can be better fitted by a pseudo-second-order model, and the adsorption process of Fe3O4@S-S/PMAA for Co(II) and Pb(II) matches well with the Freundlich isotherm equation. Notably, in the adsorption experiments, the Fe3O4@S-S/PMAA nanoparticles were demonstrated to have a maximum adsorption capacity of 48.7 mg·g-1 on Pb(II) ions with a selective adsorption order of Pb2+ > Co2+ > Cd2+ > Ni2+ > Cu2+ > Zn2+ > K+ > Na+ > Mg2+ > Ca2+ in the selective experiments. In the regeneration experiments, the Fe3O4@S-S/PMAA nanoparticles could be easily recovered by desorbing heavy metal ions from the adsorbents with eluents and showed good adsorption capacity for Co(II) and Pb(II) after eight recycles. In brief, compared to other traditional nanoadsorbents, the as-prepared Fe3O4@S-S/PMAA with improved adsorption capability and high regeneration efficiency demonstrated remarkable affinity for adsorption of Pb(II) ions, which will provide a novel technical platform for selective removal of heavy metal ions from actual polluted water.

Multisystemic Sarcoidosis Presenting With Leg Ulcers, Pancytopenia, and Polyserositis Was Successfully Treated With Glucocorticoids: A Case Report and Literature Review.

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown etiology. A variety of studies have pointed out that almost every part of the body can be affected, but it most often affected the lungs and intrathoracic lymph nodes. However, cases of sarcoidosis involving multiple organs in one patient are rarely reported. We describe a unique case of sarcoidosis, which was characterized by multiorgan involvement, including leg ulcers, splenomegaly, pancytopenia, and polyserositis. Glucocorticoids were effective during the treatment of the above lesions. This case highlights the diversity of clinical manifestations of sarcoidosis and emphasizes the importance of its differential diagnosis and the periodical follow-up. These are crucial to physicians in the diagnosis and treatment of sarcoidosis. MAIN SYMPTOMS AND IMPORTANT CLINICAL FINDINGS: A 30-year-old male complained about intermittent fever 3 years ago. A computed tomographic scan of the chest showed lymphadenopathy in the mediastinum and hilar regions. Routine blood tests showed leukopenia and mild anemia. The pathologic result of mediastinal lymph node biopsy was granulomatous lesions; thus, the patient was diagnosed with type II sarcoidosis without glucocorticoid therapy. In the following 2 years, the patient suffered from intermittent fever accompanied by dyspnea, fatigue, occasional cough, less sputum, and apparent weight loss. Abnormal physical examinations included leg ulcers and splenomegaly. Laboratory and physical tests revealed pancytopenia, polyserositis, and enlargement of lymph nodes. The pathological findings of leg ulceration, pleura, and left supraclavicular lymph node all suggested granulomas. DIAGNOSIS INTERVENTIONS AND OUTCOMES: It strongly suggested sarcoidosis since tuberculosis, lymphoma, and connective tissue disease were all excluded. Due to severe conditions and multiorgan involvement, we tried to provide methylprednisolone for this patient. After 9 months of oral glucocorticoids therapy, his subjective symptoms as well as hematological and radiological findings were all improved. His leg skin ulceration and scab were also completely disappeared. CONCLUSION: Sarcoidosis has diverse clinical presentations, and many patients present with atypical symptoms. It needs to be timely identified by the clinician and carefully differentiated from other diseases with similar findings so as to make an accurate diagnosis. In this case, the patient had a poor clinical response to glucocorticoids in the early stage of treatment due to the severe condition and multi-organ involvement. It is worth noting that the patient had improved significantly after 9 months of treatment of corticosteroids, which suggested that follow-up is critical.

Lamiophlomis herba: A comprehensive overview of its chemical constituents, pharmacology, clinical applications, and quality control.

Lamiophlomis rotata (Benth.) Kudo (LR) is an extensively used Chinese herbal medicine. It contains a variety of chemical constituents with significant biological activities that were first recorded in the classical masterpiece of Tibetan Medicine, Somaratsa. In this review, we summarize the information regarding the traditional uses, chemical constituents, pharmacological effects, clinical applications, quality control, toxicology, and pharmacokinetics of LR. At least 223 chemical constituents have been isolated from LR, including phenylethanoid glycosides, flavonoids, iridoids, volatile oils, et al. Their various physiological activities have been demonstrated as analgesic, hemostatic, anti-inflammatory, anti-tumor, marrow-supplementing, anti-bacterial, and immunity-strengthening. The clinical applications of LR and quality control are also discussed, as well as some existing problems. This article aims to provide more comprehensive information on the chemical composition, pharmacological activity, and clinical application of LR, so as to provide a theoretical basis for the further reasonable development of LR in clinical practice and of new drugs.