Transcriptomic studies unravel the molecular and cellular complexity of systemic lupus erythematosus: A review.

Transcriptomic analysis plays a vital role in investigating Systemic Lupus Erythematosus (SLE), a complex autoimmune disease characterized by diverse clinical manifestations. This approach has yielded valuable insights into gene expression patterns and molecular regulatory mechanisms involved in SLE pathogenesis. Notably, interferon-stimulated gene (ISG) signatures are significantly upregulated in immune cells, skin, and kidney. Although a correlation with serological parameters and clinical symptoms has been proposed, the association with global disease activities remains controversial. Key findings in the field include an upregulated plasmablast signature, which positively correlates with disease activity; a neutrophil signature associated with lupus nephritis; and a decreased lymphocyte signature, reflecting lymphopenia. Tissue-level studies highlight the critical role of infiltrating immune cells in organ damage. Future research should leverage advanced technologies and integrate multi-omics data to deepen our understanding of SLE's molecular underpinnings, facilitating the development of targeted therapies.

Transcriptomic Features of systemic lupus erythematosus Patients in Flare and Changes during Acute In-Hospital Treatment.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious complication of hepatic vena cava Budd-Chiari syndrome (HVC-BCS) that significantly reduces the survival time of patients. Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system. METHODS: The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed. Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups. Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical, tumor, and etiological characteristics on the total survival time of patients, and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model. The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index. RESULTS: Multivariate analysis showed that serum albumin level < 34 g/L [hazard ratio (HR) = 4.207, 95% confidence interval (CI): 1.816-8.932, P = 0.001], maximum tumor diameter > 7 cm (HR = 3.612, 95% CI: 1.646-7.928, P = 0.001), and inferior vena cava stenosis (HR = 8.623, 95% CI: 3.771-19.715, P < 0.001) were independent predictors of survival. A prognostic scoring system was developed according to the above-mentioned independent predictors, and patients were classified into grades A, B, C and D. Significant differences in survival were found among the four groups. CONCLUSIONS: This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC, which is helpful for clinical evaluation of patient prognosis.

Phylogenetic identification of symbiotic protists of five Chinese Reticulitermes species indicates a cospeciation of gut microfauna with host termites.

Symbiotic protists play important roles in the wood digestion of lower termites. Previous studies showed that termites generally possess host-specific flagellate communities. The genus Reticulitermes is particularly interesting because its unique assemblage of gut flagellates bears evidence for transfaunation. The gut fauna of Reticulitermes species in Japan, Europe, and North America had been investigated, but data on species in China are scarce. For the first time, we analyzed the phylogeny of protists in the hindgut of five Reticulitermes species in China. A total of 22 protist phylotypes were affiliated with the family Trichonymphidae, Teranymphidae, Trichomonadidae, and Holomastigotoididae (Phylum Parabasalia), and 45 protist phylotypes were affiliated with the family Pyrsonymphidae (Phylum Preaxostyla). The protist fauna of these five Reticulitermes species is similar to those of Reticulitermes species in other geographical regions. The topology of Trichonymphidae subtree was similar to that of Reticulitermes tree. All Preaxostyla clones were affiliated with the genera Pyrsonympha and Dinenympha (Order Oxymonadida) as in the other Reticulitermes species. The results of this study not only add to the existing information on the flagellates present in other Reticulitermes species but also offer the opportunity to test the hypotheses for the coevolution of symbiotic protists with their host termites.

Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), the pathogenesis of which is complicated, and it is difficult to treat. In recent years, the emerging fecal microbiota transplantation (FMT) has shown good effects in UC treatment and is therefore accepted by increasing numbers of patients. Our hospital has carried out FMT since 2017, and has achieved good results in UC treatment. We have found in our clinical work that the efficacy of re-FMT after recurrence decreased. This is difference from reported literatures. In order to attract clinical attention, here we selected typical cases for analysis. METHODS: Among all UC patients who received FMT in our hospital, 12 patients with moderate to severe UC were selected. They all received multiple FMT and were followed up for 52 weeks. Besides, none of them had other underlying diseases. Colonoscopy images of patients were presentated, SCCAI and UCDAI were used assess the effect of FMT. RESULTS: On the whole, FMT has a significant effect on moderate to severe UC. Of the 12 patients, 11 (91.7%) achieved a clinical response, 9 (75.0%) achieved clinical remission, and only one patient did not respond to FMT treatment. However, 6 patients relapsed within 52 weeks after remission, with a recurrence rate of 54.5%. Four of the six relapsed patients received FMT again, but the efficacy of FMT after relapse was significantly lower than that of the initial FMT. Fortunately, compared to before the initial FMT treatment, the severity of the disease after relapse was significantly reduced. CONCLUSION: FMT has a good effect on the relief of moderate to severe UC. However, the effect of FMT treatment after relapse is reduced. For patients who relapse after remission, the efficacy of FMT reapplication requires more experiments to verify.

Gene pathogenicity prediction of Mendelian diseases via the random forest algorithm.

The study of Mendelian diseases and the identification of their causative genes are of great significance in the field of genetics. The evaluation of the pathogenicity of genes and the total number of Mendelian disease genes are both important questions worth studying. However, very few studies have addressed these issues to date, so we attempt to answer them in this study. We calculated the gene pathogenicity prediction (GPP) score by a machine learning approach (random forest algorithm) to evaluate the pathogenicity of genes. When we applied the GPP score to the testing gene set, we obtained an accuracy of 80%, recall of 93% and area under the curve of 0.87. Our results estimated that a total of 10,384 protein-coding genes were Mendelian disease genes. Furthermore, we found the GPP score was positively correlated with the severity of disease. Our results indicate that GPP score may provide a robust and reliable guideline to predict the pathogenicity of protein-coding genes. To our knowledge, this is the first trial to estimate the total number of Mendelian disease genes.

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway.

BACKGROUND/AIMS: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. METHODS: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. RESULTS: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. CONCLUSION: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.

HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury.

BACKGROUND: Hydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. However, underlying mechanism of HSYA is not fully elucidated. The present study investigated the protective effects of HSYA in rat spinal cord compression injury model and related mechanisms involved. METHODS: Sprague-Dawley rats were divided as Sham, Control, and HSYA groups (n = 30 per group). Spinal cord injury (SCI) model was induced by application of vascular clips (force of 50 g, 1 min) to the dura at T9-T10 level of vertebra. Injured animals were administered with either HSYA (8 mg/kg at 1 and 6 h after injury, then 14 mg/kg, for a total of 7 days at 24-h time intervals) or equal volume of saline by intraperitoneal injection. RESULTS: From this experiment, we discovered that SCI in rats resulted in severe trauma, which is characterized by tissue damage, lipid peroxidation, neutrophil infiltration, inflammation mediator release, and neuronal apoptosis. However, HSYA treatment significantly reduced the following: (1) degree of tissue injury (histological score) and edema; (2) neutrophil infiltration (myeloperoxidase activity); (3) oxidative stress (superoxide dismutase, malondialdehyde, and nitric oxide); (4) pro-inflammatory cytokine expression (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2); (5) nuclear factor-κB activation; (6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining and cysteine-aspartic protease-3 activity). Moreover, in a separate set of experiments, we clearly demonstrated that HSYA treatment significantly ameliorated recovery of limb function (as evaluated by Basso, Beattie, and Bresnahan behavioral recovery scores). CONCLUSIONS: Treatment with HSYA restrains development of oxidative stress, inflammation response, and apoptotic events associated with SCI of rats, demonstrating that HSYA is a potential neuroprotectant for human SCI therapy.

Mutation Load of Multiple Ion Channel Gene Mutations in Brugada Syndrome.

Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient. The parents were heterozygous for each variation. This novel finding highlights the role of mutation load in Brugada syndrome and strongly suggests the adoption of a gene panel to obtain an accurate genetic diagnosis, which is mandatory for risk stratification, prevention, and therapy.

Exome sequencing identifies a novel mutation in GJA8 associated with inherited cataract in a Chinese family.

BACKGROUND: Congenital cataract is a clinical and genetic heterogeneous group of eye disorders that causes visual impairment and childhood blindness. In this study, a Chinese family with congenital cataract is studied. METHODS: In order to identify the genetic defects which were associated with congenital cataract, a whole-exome sequencing approach is performed to screen for the potential mutation-causing disease. RESULTS: The result revealed a novel heterozygous mutation (c.433G > T; p.G145W) in exon 2 the of GJA8 gene, which can be detected in all affected individuals, but not the unaffected family members. Meanwhile, this novel mutation cannot be retrieved in 100 healthy local Chinese controls and five other SNPs databases (dbSNP, ESP, ExAC, HTD and HGVD). Moreover, p.G145W was predicted as a mutation with pathogenicity by using bioinformatics methods, including PolyPhen-2, SIFT, PROVEAN, SNPs3D and the mutation significance cutoff (MSC). However, molecular function analysis of this novel mutation (p.G145W, GJA8) indicated that it did not affect the subcellular distributions and the trafficking of GJA8 protein to the plasma membrane. The truth of pathogenic significance with this novel mutation in GJA8 gene needed to be further studied. CONCLUSIONS: The c.433G > T (p.G145W) mutation in the GJA8 gene was first reported to our best knowledge. The results of our study would further broaden the mutation spectrum of GJA8 associated with congenital cataract.

[Study on the Prediction of Germination Rate of Rice Seeds with Continuous Polarization Spectroscopy].

With respect to the problem of long period and low precision in using traditional methods to predict rice seeds germination rate, a novel method based on continuous polarization spectroscopy was proposed to achieve rapid and nondestructive prediction .The paper set different aging rice seeds as prediction targets and ten minutes as prediction time, using polarizer to modulate optical fiber collimating light source to linearly polarized light which issuing into rice seeds extract vertically before rotating the analyser every 5 degrees . The transmission spectrum was predicted through the optical fiber spectrometer. After normalization pretreatment to the polarization spectrum, the article gave the characteristics of polarization angel and wavelength by 0 degree, 5 degrees, 25 degrees, 620, 788 and 576 nm according to the contribution of polarization angel and wavelength when predicting different germination rate rice seeds and inputted obtained continuous polarization spectrum by wavelength, polarization angel, transmissivity to construct rice seeds germination rate prediction model using three modeling methods to build rice seeds germination rate prediction model in comparison, including Partial Least Squares Regression (PLSR), Back Propagation Neural Network (BPNN) and Radial Basis Function Neural Network (RBFNN).1 520 sets of experimental data were measured in total at different polarization angels through using rice seeds with different aging days (0, 2, 4, 6) respectively, setting 912 sets of data as calibration set and 608 sets of data as predicion set. The modeling results show that RBF model's prediction accuracy is the highest. Its correlation coefficient is 0.976; the mean square is 0.785; and the average relative error is 0.85%. The research results show that the continuous polarization spectroscopy technique through multidimension spectral information can achieve rapid and accurate prediction of rice seeds germination rate.

Apoptosis associated with Wnt/ß-catenin pathway leads to steroid-induced avascular necrosis of femoral head.

BACKGROUND: The objective of the current study was to establish a rat model to investigate apoptosis in steroid-induced femoral head osteonecrosis occurring via the Wnt/ß-catenin pathway. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into a control group (group A), model group (group B) and sFRP1 group (group C), each consisting of 24 rats, and the rats were intravenously injected with LPS (10 µg/kg body weight). After 24 h, three injections of MPS (20 mg/kg body weight) were administered intramuscularly at 24-h intervals. The rats in group C were injected intramuscularly with 1 µg/kg sFRP1 protein per day for 30 days, beginning at the time of the first MPS administration. The group A rats were fed and housed under identical conditions but received saline injection. All animals were sacrificed at weeks 2, 4 and 8 from the first MPS injection. Histopathological staining was preformed to evaluated osteonecrosis. Apoptosis was detected via quantitative terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick-end labelling (TUNEL) staining, caspase-3 activity assay, and detection of Bcl-2 and Bax protein expression by immunohistochemistry and Western blotting. Wnt/ß-catenin pathway signalling molecules, including activated ß-catenin and c-Myc, were detected by immunohistochemistry and Western blotting. RESULTS: Typical osteonecrosis was observed in groups B and C. Apoptosis gradually increased with increasing time in both groups B and C. More severe osteonecrosis and apoptosis were observed in group C compared with group B. The expression levels of caspase-3 and Bax were higher while that of Bcl-2 was lower in group C compared with group B. The expression levels of activated ß-catenin and c-Myc gradually decreased with increasing time in both groups B and C, and they were lower in group C compared with group B. CONCLUSIONS: The Wnt/ß-catenin pathway is involved in the pathogenesis of early stage SANFH, as we have demonstrated in an SANFH rat model, and it may act through the regulation of c-Myc, which affects the cell cycle and cell apoptosis.

Partial greater trochanter osteotomy for hip reduction in total hip arthroplasty for high dislocated hip: a preliminary report.

BACKGROUND: Hip reduction in total hip arthroplasty for high dislocated hips is difficult. Various femur osteotomy procedures have been used for hip reduction, but these methods increase operative time and risk of nonunion. We investigated the efficacy of a novel partial greater trochanter osteotomy technique for hip reduction in total hip arthroplasty for patients with high hip dislocation. METHODS: Twenty-one patients (23 hips) with high dislocated hip were treated with total hip arthroplasty that included partial greater trochanter osteotomy, i.e., the upper 2/3 greater trochanter was resected, and the gluteus medius muscle attachment was spared. The clinical outcome was evaluated by comparing the Harris hip scores and radiographic exam results, obtained before surgery and at follow-ups. RESULTS: Follow-ups of 21 patients ranged from 13 to 56 months. The mean Harris hip score increased from preoperative 55.0 (36-69) to postoperative 86.1 (71-93; P = 0.00). The average preoperative leg length discrepancy in patients with unilateral high hip dislocation was 46 mm (28-65 mm); postoperatively leg length discrepancy was less than 1 cm in 11 patients, between 1 and 2 cm in 8 patients, and more than 2 cm in 2 patients. The average leg lengthening at the time of surgery was 36 mm (24-54 mm). Trendelenburg's gait changed from positive to negative in 20 hips by the last follow-up. No nerve injury occurred postoperative. CONCLUSION: Partial greater trochanter osteotomy is an effective method to render hip reduction in total hip arthroplasty for patients with high dislocation of the hip.

[Progress in the physiological and pathophysiological functions of sodium calcium exchangers].

Sodium calcium exchanger (NCX), which is widely expressed in the plasma membrane, mitochondrial membrane and secretory vesicles in diverse kinds of cells, belongs to a type of cation translocators. NCX works in two modes, the forward mode and reverse mode, to regulate the intracellular Ca(2+) concentration bi-directionally. In the forward mode, NCX carries Ca(2+) out of the cell against its electrochemical gradients coupled to the influx of Na(+) down its electrochemical gradients; alternatively, Ca(2+) enters through the reverse mode of NCX, and Na(+) is carried out of the cell. Exactly through the two-way modes, NCX can regulate intracellular Ca(2+) concentration fleetly and accurately, and plays a critical role in a series of physiological processes including intracellular signal transduction, growth and development of cells, excitation and its coupled functions of excitable cells. NCX are acknowledged to be involved in myofiber contraction, neurotransmission, migration and differentiation of neurogliocyte, activation of immune cells, secretion of cytokines and hormones etc. Moreover, abnormal activation of the reverse mode of NCX plays a vital role in many pathological processes including cell apoptosis, ischemia-reperfusion injury, insulin secretion, tumor etc. Here we reviewed the research status about the NCX's participation in some physiological and pathophysiological processes, so as to provide comprehensive understanding about its functions.

Effect of Body Weight Support Training on Lower Extremity Motor Function in Patients With Spinal Cord Injury: A Systematic Review and Meta-analysis.

OBJECTIVES: The aims of the study are to systematically evaluate the effect of body weight support training on lower extremity motor function(s) in patients with spinal cord injury and to compare the effect differences among three body weight support training methods. DESIGN: PubMed, Web of Science, Cochrane Library, Embase, CNKI, CBM, China Scientific Journal, and Wan Fang databases were searched until December 31, 2022. Meta-analysis and network meta-analysis were conducted using RevMan 5.4 and ADDIS 1.16.8. RESULTS: Nineteen randomized controlled trials involving 864 patients were included. The meta-analysis showed that body weight support training could improve lower extremity motor scores according to the International Standards for Neurological Classification of Spinal Cord Injury standard (mean difference = 6.38, 95% confidence interval = 3.96-8.80, P < 0.05), walking speed (standard mean difference = 0.77, 95% confidence interval = 0.52-1.02, P < 0.05), and modified Barthel Index scores (mean difference = 9.85, 95% confidence interval = 8.39-11.30, P < 0.05). The network meta-analysis showed no significant difference among the three body weight support training methods for improving lower extremity motor scores in patients with spinal cord injury. The best probability ranking of the body weight support training methods for improving lower extremity motor scores in patients with spinal cord injury was robot-assisted gait training ( P = 0.60), followed by aquatic exercise ( P = 0.21) and body weight support training ( P = 0.19). CONCLUSIONS: Body weight support training can improve lower extremity motor score in patients with spinal cord injury. No significant difference was observed among the three body weight support training methods, but robot-assisted gait training may produce the best effect.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Synthesis and antitumor activity of 1,3,4-oxadiazole possessing 1,4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors.

A series of 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (7a-7q) have been designed, synthesized and evaluated for their antitumor activity. Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity. Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive control. The results of apoptosis and flow cytometry (FCM) demonstrated that compound 7a induce cell apoptosis by the inhibition of MetAP2 pathway. Molecular docking was performed to position compound 7a into MetAP2 binding site in order to explore the potential target.

Atorvastatin attenuates bleomycin-induced pulmonary fibrosis via suppressing iNOS expression and the CTGF (CCN2)/ERK signaling pathway.

Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA) level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS) in lung tissues and, thus, prevented nitric oxide (NO) release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2)) and phosphorylation extracellular regulated protein kinases (p-ERK) expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2)/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.

[Study on fingerprint of xiaochaihu granules sold in the market].

To establish a fingerprint of Xiaochaihu granules sold in the market with HPLC method, and study fingerprints of Xiaochaihu granules produced by different manufacturers and in different batches of the same manufacturer. Seven major index components were identified for the first time. The established method provided an all-around analysis on the quality assessment of Xiaochaihu granules.

[Regulation effects of intracellular and extracellular Ca2+ on biosynthesis of rosmarinic acid induced by salicylic acid in young seedlings of Salvia miltiorrhiza].

OBJECTIVE: To investigate the effect of intracellular and extracellular Ca2+ on the biosynthesis of rosmarinic acid (RA) induced by salicylic acid in young seedlings of Salvia miltiorrhiza. METHOD: Young seedlings of S. miltiorrhiza were used to select an optimal concentration of salicylic acid (SA), and then use the optimal concentration of SA to investigate the effects of extracellular Ca2+ channel inhibitors Verapamil, LaCl3, intracelluar calmodulin antagonist TFP and intracelluar Ca2+ channel inhibitors LiCl on the biosynthesis of RA and related enzymes. RESULT: SA increased the accumulation of RA and the activities of PAL and TAT, especially the SA of 2 mmol x L(-1) after 24 h. SA improved the accumulation of RA to (40.51 +/- 2.16) mg x g(-1), which was 1.97 times than that of control, and the activities of PAL, TAT were 1.42 times and 1.29 times than those of the control. However, Vp, LaCl3, TFP, LiCl inhibited the effects of SA evidently. CONCLUSION: Ca2+ plays a key role in the regulation of the induction process.