Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report.

BACKGROUND: Monomorphic epithelial intestinal T-cell lymphoma (MEITL) is a rare type of peripheral T-cell lymphoma. The clinical manifestations are diarrhea, abdominal pain, perforation and an abdominal mass. CASE SUMMARY: We present a 52-year-old female patient who was diagnosed with MEITL. Further disease progression was observed after multiline chemotherapy. Eventually, the patient died of a severe infection. CONCLUSION: MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior, a high risk of severe life-threatening complications, and a poor prognosis.

Silver Metal-Organic Framework Derived N-Doped Carbon Nanofibers for CO2 Conversion into ß-Oxopropylcarbamates.

Developing efficient heterogeneous catalysts for chemical fixation of CO2 to produce high-value-added chemicals under mild conditions is highly desired but still challenging. Herein, we first reported an approach to prepare a novel catalyst (Ag@NCNFs), featuring Ag nanoparticles (NPs) embedded within porous nitrogen-doped carbon nanofibers (NCNFs), via growing a Ag metal-organic framework on one-dimensional electrospun nanofibers followed by pyrolysis. Benefiting from the abundant nitrogen species and porous structure, Ag NPs is well dispersed in the obtained Ag@NCNFs. Catalytic studies indicated that Ag@NCNFs exhibited excellent catalytic activity for the three-component coupling reaction of CO2, secondary amines, and propargylic alcohols to generate ß-oxopropylcarbamates under mild conditions with a turnover number (TON) of 16.2, and it can be recycled and reused at least 5 times without an obvious decline in catalytic activity. The reaction mechanism was clearly clarified by FTIR, NMR, 13C isotope labeling, control experiments, and density functional theory calculations. The results suggest that Ag@NCNFs and 1,8-diazabicyclo[5.4.0]undec-7-ene can synergistically activate propargylic alcohol to react with CO2, and then the generated α-alkylidene cyclic carbonate was invaded by secondary amine to produce ß-oxopropylcarbamate. Importantly, to the best of our knowledge, this is the first experimental and theoretical investigation on this reaction.

Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive non-Hodgkin's lymphoma (NHL), accounting for 30%-40% of adult NHLs. This report aims to explore the efficacy and safety of rituximab combined with Bruton tyrosine kinase inhibitors (BTKis) in the treatment of elderly patients with DLBCL. CASE SUMMARY: The clinical data of two elderly patients with DLBCL who received rituximab combined with BTKi in our hospital were retrospectively analyzed, and the literature was reviewed. The patients were treated with chemotherapy using the R-miniCHOP regimen for two courses. Then, they received rituximab in combination with BTKi. CONCLUSION: The treatment experience in these cases demonstrates the potential efficacy of rituximab combined with BTKi to treat elderly DLBCL patients, thus providing a new treatment strategy.

Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration.

Aims: This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods: The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results: A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF-gene interaction and TF-miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion: The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets.

A Case of Multiple Myeloma-Associated Systemic Amyloidosis with Multiple Skin Manifestations as the First Symptom.

An 81-year-old woman presented with purpura, petechiae, ecchymoses, flesh or brown-colored waxy, smooth, papules, warty plaque, nail dystrophy and palmodigital erythematous swelling for more than 6 years. She was diagnosed as multiple myeloma-associated systemic amyloidosis after skin subcutaneous histopathological examinations and relevant examinations such as blood and bone marrow. Systemic amyloidosis is closely related with multiple myeloma (MM). Multiple and pleomorphic skin lesions are not usual among patients with multiple myeloma or systemic amyloidosis.

Highly Efficient Conversion of Aziridines and CO2 Catalyzed by Microporous [Cu12] Nanocages.

The conversion of CO2 as a C1 source into value-added products is an attractive alternative in view of the green synthesis. Among the reported approaches, the cyclization reaction of aziridines with CO2 is of great significance since the generated N-containing cyclic skeletons are extensively found in pharmaceutical chemistry and industrial production. However, a low turnover number (TON) and homogeneous catalysts are often involved in this catalytic system. Herein, one novel copper-organic framework {[Cu2(L4-)(H2O)2]·3DMF·2H2O}n (1) (H4L = 2'-fluoro-[1,1':4',1″-Terphenyl]-3,3″,5,5″-tetracarboxylic acid) assembled by nanosized [Cu12] cages was successfully synthesized and structurally characterized, which exhibits high CO2/N2 selectivity due to the strong interactions between CO2 and open Cu(II) sites and ligands in the framework. Catalytic investigations suggest that 1 as a heterogeneous catalyst can effectively catalyze the cyclization of aziridines with CO2, and the TON can reach a record value of 90.5. Importantly, 1 displays excellent chemical stability, which can be recycled at least five times. The combination explorations of nuclear magnetic resonance (NMR), 13C-isotope labeling experiments, and density functional theory (DFT) clearly uncover the mechanism of this aziridine/CO2 coupling reaction system, in which 1 and tetrabutylammonium bromide (TBAB) can highly activate the substrate molecule, and the synergistic catalytic effect between them can greatly reduce the reaction energy barrier from 51.7 to 36.2 kcal/mol.

Liangxue Jiedu Runzhi ointment in the treatment of mild and moderate psoriasis with blood-heat syndrome: A double-blind randomized controlled trial.

INTRODUCTION: Psoriasis is a kind of chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales and keratinocyte hyperproliferation. Psoriasis Vulgaris, the most common kind of psoriasis, severely deteriorates the life quality of patients. Traditional Chinese Medicine (TCM) is a good choice for the treatment of psoriasis, which has been proved to be safe and effective, and may reduce the recurrence rate. In clinical practice, Liangxue Jiedu Runzhi (LJR) ointment can effectively treat mild and moderate psoriasis with blood-heat syndrome, but there is a lack of evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of LJR ointment for the treatment of mild and moderate psoriasis with blood-heat syndrome. METHODS: A multicenter, randomized, double-blind, placebo-controlled, and self-controlled clinical trial was carried out according to this paper. The symmetrical rashes of each subject were regarded as the target lesions and were randomly divided into a treatment group (LJR ointment group) and a control group (placebo group). The LJR ointment or placebo ointment were externally administered on bilateral symmetric rashes, twice a day for eight weeks. The follow-up examination was made for subjects every two weeks. The primary research finding was conveyed by Psoriasis Area and Severity Index (PASI) in 8 weeks. The secondary research finding includes adverse events. RESULTS: 46 subjects undergo this research project. The difference between PASI scores of the target lesions in the treatment group and control group is statistically significant were in 8 weeks (P < .001). The percentage of PASI 75 in treatment group and control group were 48% and 15% in week 8, respectively (x2 = 11.33, P < .05). No severe adverse events were reported. CONCLUSIONS: LJR ointment was proved to have efficacy in the treatment of mild and moderate psoriasis with the blood-heat syndrome.

Galectin­1 binds GRP78 to promote the proliferation and metastasis of gastric cancer.

The present study aimed to investigate the potential molecular mechanisms by which galectin­1 (Gal­1) and glucose­regulated protein 78 (GRP78) influence the development of malignant gastric cancer (GC). Immunohistochemistry and western blotting were used to map the expression and location of the Gal­1 gene in the 80 paraffin­embedded GC samples, 16 fresh samples and surrounding tissues. Gal­1 was overexpressed and knocked down using lentiviral vectors in the human GC cell lines HGC­27 and AGS. Through the use of the Cell Counting Kit­8 assay, clone formation assay, wound healing assay, invasion assay and tumor xenograft, the possible biological roles of Gal­1 were further evaluated. The downstream interacting proteins were predicted by the BioGRID database, and GRP78 was chosen for further investigation. Immunofluorescence labeling and Co­IP were used to confirm the connection. The statistical tests utilized were the two­tailed paired Student's t­test, χ2 test, Kaplan­Meier and Cox regression analysis, and Spearman's rank correlation coefficients. In GC, Gal­1 is extensively expressed and has the potential to interact with GRP78. Poor prognosis is linked to high levels of GRP78 and Gal­1 expression in patients with GC. According to the functional study, Gal­1 knockdown prevented cells from thriving and pushed Gal­1 expression, which aided in the proliferation, migration and invasion of GC. Gal­1 overexpression additionally aided the development of subcutaneous xenograft tumors. The mechanistic investigation proved that GRP78 and Gal­1 interacted, accelerating the course of GC. Gal­1 silencing had an inhibitory effect on the proliferation of HGC­27 cells that was removed by ectopic GRP78 expression, whereas the stimulating effects of Gal­1 overexpression in AGS cells were inhibited by GRP78 knockdown. In conclusion, Gal­1 interacts with GRP78 to facilitate the advancement of GC. The Gal­1/GRP78 axis is supported by the functional data of the present study as a possible GC treatment target.

Refractory lymphoma treated with chimeric antigen receptor T cells combined with programmed cell death-1 inhibitor: A case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive non-Hodgkin's lymphoma (NHL), accounting for 30%-40% of adult NHL. Primary testicular (PT) lymphoma is an uncommon extranodal disease representing approximately 1%-2% of lymphoma. Approximately 30%-40% of patients are refractory to frontline therapy or relapse after complete remission. Refractory DLBCL responds poorly to other lines of chemotherapy, and experiences short-term survival. CASE SUMMARY: We present a 41-year-old male patient who was diagnosed with PT-DLBCL. Further disease progression was observed after multiline chemotherapy. Chimeric antigen receptor T cells (CAR-T) therapy salvaged the patient. Unfortunately, a new mass was observed in the right adrenal area after six months. The patient was administered programmed cell death protein-1 (PD-1) inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up. CONCLUSION: Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.

Role of Nrf2 and HO-1 in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common age-related disease with clinical manifestations of lumbar and leg pain and limited mobility. The pathogenesis of IDD is mainly mediated by the death of intervertebral disc (IVD) cells and the imbalance of extracellular matrix (ECM) synthesis and degradation. Oxidative stress and inflammatory reactions are the important factors causing this pathological change. Therefore, the regulation of reactive oxygen species and production of inflammatory factors may be an effective strategy to delay the progression of IDD. In recent years, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream regulated protein heme oxygenase-1 (HO-1) have received special attention due to their antioxidant, anti-inflammatory and anti-apoptotic protective effects. Recent studies have elucidated the important role of these two proteins in the treatment of IDD disease. However, Nrf2 and HO-1 have not been systematically reported in IDD-related diseases. Therefore, this review describes the biological characteristics of Nrf2 and HO-1, the relationship between Nrf2- and HO-1-regulated oxidative stress and the inflammatory response and IDD, and the progress in research on some extracts targeting Nrf2 and HO-1 to improve IDD. Understanding the role and mechanism of Nrf2 and HO-1 in IDD may provide novel ideas for the clinical treatment and development of Nrf2- and HO-1-targeted drugs.

Historical review of malaria control and elimination in the border areas of China: A case study of Yunnan Province.

To understand how malaria could be eliminated in the original hyperendmic area for malaria along international borders in Yunnan Province, malaria situation and control were described on the basis of seven phases. At last the experiences and lessons of the program that reduced border malaria from hyperendmicity to malaria-free status were summarized. Malaria control and elimination area were particularly difficult in the Yunnan border. The achievement can be attributed to high political commitment, strategic and technical innovations based on the actual locality, effective collaboration and communication with neighbouring countries to carry out cross border interventions. Other border areas might perform their own pilot interventions based on their local context, including malaria burden, governing system, health service structure contextualized based on their socioeconomic development and ecology, and then a local decision could be made according to their own trial results.

The Haoqin-Huaban formula alleviates UVB-induced skin damage through HOXA11-AS-mediated stabilization of EZH2.

Exposure of skin to ultraviolet B (UVB) irradiation induces oxidative damage, immune suppression, inflammation, and skin cancer. Recently, an increase in the use of traditional Chinese medicine decoction with antioxidant properties has emerged as protection for skin tissues against UVB-induced damage. The aim of this study was to investigate mechanisms of the protective effect of the Haoqin-Huaban formula (HQHB) on UVB-induced skin damage. First, cell survival, apoptosis, and oxidative stress were evaluated upon UVB irradiation in the presence of HQHB using HaCaT cells and mice as model systems. Subsequently, bioinformatic analyses, RNA pulldown assays, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation were conducted to verify the regulation among HQHB, hypoxia-inducible factor 1α (HIF-1α), HOXA11-AS and enhancer of zeste homolog 2 (EZH2) in HaCaT cells. In this study, we found that administration of HQHB inhibited, in a dose-dependent manner, UVB-induced skin damage by eliminating oxidative stress. HQHB was found to upregulate HOXA11-AS expression by activating HIF-1α. Furthermore, HOXA11-AS stabilized the EZH2 protein by inhibiting its ubiquitination and proteasomal degradation. Consequently, rescue assays demonstrated that HOXA11-AS promoted proliferation and inhibited apoptosis in HaCaT cells by reducing oxidative stress. Taken together, our results help to elucidate the function and regulatory mechanism of HQHB in reducing UVB-induced skin damage.

Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration.

BACKGROUND: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action. METHODS: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-ß-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16). RESULTS: Pretreatment with PACs exhibited protective effects against IL-1ß-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1ß-treated NP cells. SA-ß-gal staining showed that IL-1ß-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1ß-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment. CONCLUSION: The results of the present study showed that PACs inhibit IL-1ß-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.

Clinical trait-connected network analysis reveals transcriptional markers of active psoriasis treatment with Liangxue-Jiedu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a complex recurrent inflammatory skin disease with different pathological changes in different stages. Psoriasis in its active stage, which is comparable to the blood-heat type in traditional Chinese medicine (TCM), has been treated by Liangxue Jiedu Decoction (LJD) in TCM for decades, with proven efficacy. According to TCM theories, LJD has the function of removing heat and pathogenic factors from the blood. AIM OF THE STUDY: We aimed to investigate the molecular features associated with the active stage psoriasis and identify genes responding to LJD treatment accompanied by lesion remission. MATERIALS AND METHODS: Healthy volunteers and psoriasis patients who met specific diagnostic criteria were recruited. Twenty-six transcriptomes were profiled from the peripheral blood mononuclear cells (PBMCs) of 10 psoriasis patients (pre- and post-treatment) and 6 healthy volunteers. RNA sequencing data were analyzed using an integrated approach combining differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA), by which gene expression was linked to multiple clinical traits, including psoriasis area and severity index (PASI), as well as the improvement rate of skin lesions (ΔPASI). The actions of LJD were then verified using an in vitro cell assay coupled to flow cytometric analysis and RT-PCR. RESULTS: We identified four network modules with statistical significance (P < 0.05), two of which connected to the PASI score, while the other two connected to 8-week treatment and ΔPASI, respectively. In psoriasis patients, activated inflammatory pathways and inhibited G-protein signaling genes (GTPase IMAP family member and G protein-coupled receptor) co-occurred, with high expression of CD83 and CD69, and low expression of CD160 and CD180, compared with the health. Accompanying LJD treatment and lesion remission, the expression of CD69 and cell cycle-related genes, including CCNA2, CCNB2, CDK1, and TOP2A, was down-regulated. The inhibitory role of LJD on CD69 expression was confirmed by the decline of activating naïve CD4+ T lymphocytes. CONCLUSION: Our study suggests that active psoriasis is characterized by unbalanced immune status with dendrite cell and lymphocyte-associated inflammatory activation as well as NK cell- and B cell-associated defense response aberrance. LJD played an inhibitory role in T cell activation, a process located downstream pathological cascade of psoriasis.

Development and Validation of a Hypoglycemia Risk Model for Intensive Insulin Therapy in Patients with Type 2 Diabetes.

AIMS: To develop a simple hypoglycemic prediction model to evaluate the risk of hypoglycemia during hospitalization in patients with type 2 diabetes treated with intensive insulin therapy. METHODS: We performed a cross-sectional chart review study utilizing the electronic database of the Third Affiliated Hospital of Sun Yat-sen University, and included 257 patients with type 2 diabetes undergoing intensive insulin therapy in the Department of Endocrinology and Metabolism. Logistic regression analysis was used to derive the clinical prediction rule with hypoglycemia (blood glucose ≤ 3.9 mmol/L) as the main result, and internal verification was performed. RESULTS: In the derivation cohort, the incidence of hypoglycemia was 51%. The final model selected included three variables: fasting insulin, fasting blood glucose, and total treatment time. The area under the curve (AUC) of this model was 0.666 (95% CI: 0.594-0.738, P < 0.001). CONCLUSIONS: The model's hypoglycemia prediction and the actual occurrence are in good agreement. The variable data was easy to obtain and the evaluation method was simple, which could provide a reference for the prevention and treatment of hypoglycemia and screen patients with a high risk of hypoglycemia.

Traditional Chinese medicine for psoriasis vulgaris: A Protocol of a prospective, multicenter cohort study.

INTRODUCTION: The incidence of psoriasis vulgaris is increasing worldwide. Chronic recurrence of the disease, as well as accompanying cardiovascular disease, metabolic syndrome, and depression has affected the physical and mental health of these patients. Psoriasis vulgaris is a difficult and major disease in the dermatology field. Short-term curative effects using conventional therapy for psoriasis vulgaris has made major strides. However, traditional Chinese medicine (TCM) treatment has long-term curative advantages for psoriasis vulgaris but lacks the scientific and clinical evidence for its use. This study intends to demonstrate and provide scientific and clinical evidence for the use of TCM to delay the recurrence of psoriasis vulgaris. METHODS AND ANALYSIS: This will be a prospective, multicenter cohort study. We intend to recruit 1521 psoriasis vulgaris patients from 14 hospitals in Beijing, Tianjin, and Hebei. Treatment will be based on the diagnosis specifications and clinical practice guidelines of TCM and conventional therapy. During inclusion and the subsequent follow-up period, doctors through electronic case reports will collect different therapeutic TCM regimens and conventional therapy that were administered. Information on life condition, skin lesions at each visit, World Health Organization Quality of Life Instruments, Zung Self-rating Anxiety Scale, Zung Self-assessment of Depression, laboratory examinations, incidence of new rash and recurrence during the remission and recurrence stages will be recorded. ETHICS AND DISSEMINATION: The clinical trial protocol for this study was approved by the ethics committee of the Beijing hospital of TCM affiliated to capital medical university (Ethics number: 2019BL02-010-02). We will publish and present our results at national and international conferences and in peer-reviewed journals specialized in dermatology. TRIAL REGISTRATION: This protocol has been registered in clinicaltrials. gov (ChiCTR1900021629).

Efficacy and Safety of Jueyin Granules for Patients with Mild-to-Moderate Psoriasis Vulgaris: Protocol for a Multicenter Randomized Placebo-Controlled Trial.

Introduction. The etiology and pathogenesis of psoriasis are complex. Blood-heat syndrome is the core pathogenesis of psoriasis. Based on theories of Chinese medicine (CM), heat-clearing and blood-cooling (HCBC) are the primary treatment. Very few studies have investigated the pharmacological mechanism of the CM HCBC method for treating psoriasis. This multicenter randomized controlled trial will focus on treating psoriasis blood-heat syndrome with the HCBC method using Jueyin granules (JYKL). This will be an objective and standardized evaluation of the efficacy, safety, and reproducibility of the HCBC method to obtain objective evidence meeting international standards that aim to establish a clinical standard suitable for the popular application of CM for treating psoriasis. Methods and Analysis. A five-center randomized double-blind placebo-controlled clinical design will be used in this study. At least 196 participants will be randomly assigned to receive either JYKL or placebo treatment approximately 30 minutes after meals in the morning and evening (one sachet per time, twice daily for 8 consecutive weeks). The study duration will be 17 weeks, including 1 week of screening, 8 weeks of intervention, and 8 weeks of follow-up. The patients will be evaluated every 2 weeks, and the measures will be compared with baseline values. The primary outcome measure will be the psoriasis lesion area severity index. We will also observe the recurrence rate, body surface area, physician global assessment, dermatology life quality index, quality of life index, visual analogue scale score, CM symptom score, combined drug use, and adverse events. This trial is registered with NCT03961230.

Effects of luteolin on treatment of psoriasis by repressing HSP90.

AIMS: This study was conducted to further clarify the efficacy and potential of luteolin in treating psoriasis and to explore its inner mechanisms. METHODS: A pharmacology network displayed the construction of a drug disease target prediction method. The prediction technique was validated via cell experiments in vitro and animal experiments in vivo, respectively. The effects of IFN-γ and luteolin were detected in HaCaT cells. The secretion of exosome and expression of mRNA and protein were detected to explain the relationship between luteolin's regulation of HSP90 (HSP90α and HSP90ß) activity in vitro. An in vivo psoriasis mouse model was established to further explore the efficacy of luteolin. Morphological and histological changes in skin lesions were observed, and the CD63, calnexin, Hsp90α, and Hsp90ß protein expression was analyzed. Peripheral blood mononuclear cells (PBMCs) were separated and detected via flow pattern analysis to determine how luteolin effects the immune cells in a psoriasis model. RESULTS: Luteolin as a candidate compound is predicted to have a molecular-target correspondence with HSP90 according to a pharmacology network analysis. Cell experiments indicated that the pathogenesis of psoriasis was significantly related to the increase in IFN-γ, which promoted the transcriptional expression and exosome secretion of HSP90 in HaCaT cells; conversely, luteolin inhibited those and alleviated the promotion of IFN-γ. The effect of luteolin on HSP90 was slightly weaker than that of INF-γ. Animal experiments indicated that the efficacy of luteolin was similar to that of 17-AAG, which both alleviated skin tissue lesions and symptoms, improved the expression of Hsp90 mRNA and protein in skin tissue, and promoted exosome secretion of Hsp90 in plasma. For immune cells in mice with psoriasis, luteolin reduced the proportion of Th1/Th2 and Th17/Treg and inhibited the increase in Th1 and Th17 in the peripheral blood. CONCLUSION: Luteolin can relieve the lesions and symptoms of psoriasis through reversing the effects of IFN-γ, inhibiting the expression and exosome secretion of HSP90, and regulating the proportion of immunocytes. Therefore, this study provides the possible mechanisms and potential utilization of luteolin as a novel treatment for psoriasis.

Genetic polymorphism of merozoite surface proteins 1 and 2 of Plasmodium falciparum in the China-Myanmar border region.

BACKGROUND: Malaria is a major public health problem in the China-Myanmar border region. The genetic structure of malaria parasite may affect its transmission model and control strategies. The present study was to analyse genetic diversity of Plasmodium falciparum by merozoite surface proteins 1 and 2 (MSP1 and MSP2) and to determine the multiplicity of infection in clinical isolates in the China-Myanmar border region. METHODS: Venous blood samples (172) and filter paper blood spots (70) of P. falciparum isolates were collected from the patients of the China-Myanmar border region from 2006 to 2011. The genomic DNA was extracted, and the msp1 and msp2 genes were genotyped by nested PCR using allele-specific primers for P. falciparum. RESULTS: A total of 215 P. falciparum clinical isolates were genotyped at the msp1 (201) and msp2 (204), respectively. For the msp1 gene, MAD20 family was dominant (53.49%), followed by the K1 family (44.65%), and the RO33 family (12.56%). For the msp2 gene, the most frequent allele was the FC27 family (80.93%), followed by the 3D7 family (75.81%). The total multiplicity of infection (MOI) of msp1 and msp2 was 1.76 and 2.21, with a prevalence of 64.19% and 72.09%, respectively. A significant positive correlation between the MOI and parasite density was found in the msp1 gene of P. falciparum. Sequence analysis revealed 38 different alleles of msp1 (14 K1, 23 MAD20, and 1 RO33) and 52 different alleles of msp2 (37 3D7 and 15 FC27). CONCLUSION: The present study showed the genetic polymorphisms with diverse allele types of msp1 and msp2 as well as the high MOI of P. falciparum clinical isolates in the China-Myanmar border region.