Photoinduced Palladium-Catalyzed Radical Heck-Type Coupling of Cyclobutanone Oxime Esters with Vinyl Arenes.

A palladium-catalyzed radical Heck-type coupling reaction of cyclobutanone oxime esters with olefins under visible-light irradiation has been developed. The cyanoalkyl/Pd(I) hybrid species generated by selected ring-opening C-C bond cleavage of imino/Pd(I) species reacted smoothly with vinyl arenes, delivering the cyanoalkylation olefins under mild conditions. This elegant strategy has a broad scope and functional group tolerance. Subsequently, late-stage functionalization of bioactive molecules and synthetic transformations of the product further confirm the practicality.

The effect of cognition in combination with an ACBT on dyspnea-related kinesiophobia in patients with moderate to severe COPD: Quasirandomized controlled trial study.

Patients with moderate to severe COPD frequently experience dyspnea, which causes these patients to acquire a fear of dyspnea and a fear of activity. This study developed a cognitive intervention combined with active cycle of breathing technique (ACBT) intervention program based on the fear-avoidance model, with the goal of evaluating the program's effectiveness in improving dyspnea-related kinesiophobia in patients with moderate to severe COPD. This study had a total of 106 participants. For 8 weeks, the intervention group (N=53) received cognitive combined with ACBT, while the control group (N=53) received standard care. The findings of the four times the dyspnea belief questionnaire were collected indicated that the combined intervention had a better impact on reducing dyspnea-related kinesiophobia than did routine nursing (P<0.05), and the impact persisted even after the intervention. Additionally, it may enhance dyspnea and quality of life, increase exercise capacity, and lower the BODE index.

Physical activity and chronic obstructive pulmonary disease: a scoping review.

BACKGROUND: Reduced physical activity (PA) was the strongest predictor of all-cause mortality in patients with chronic obstructive pulmonary disease (COPD). This scoping review aimed to map the evidence on the current landscape of physical activity, barriers and facilitators, and assessment tools across COPD patients. METHODS: Arksey and O'Malley's scoping review methodology framework guided the conduct of this review. An electronic search was conducted on five English databases (PubMed, Cochrane Library, PsycINFO, CINAHL and Web of Science) and three Chinese databases (CNKI, CQVIP and WAN-FANG) in January 2022. Two authors independently screened the literature, extracted the studies characteristics. RESULTS: The initial search yielded 4389 results, of which 1954 were duplicates. Of the remaining 135 articles, 42 studies met the inclusion criteria. Among the reviewed articles, there were 14 (33.3%) cross-sectional study, 9 (21.4%) cohort study, 4 (9.5%) longitudinal study, 3 qualitative study, 12 (28.7%) randomized control trials. The main barriers identified were older age, women, lung function, comorbidities, COPD symptoms (fear of breathlessness and injury, severe fatigue, anxiety and depression), GOLD stage, frequency of exacerbation, oxygen use, lack of motivation and environment-related (e.g., season and weather). Twelve studies have evaluated the effects of physical exercise (e.g., walking training, pulmonary rehabilitation (PR), pedometer, self-efficacy enhancing intervention and behavioral modification intervention) on PA and showed significant positive effects on the prognosis of patients. However, in real life it is difficult to maintain PA in people with COPD. CONCLUSIONS: Changing PA behavior in patients with COPD requires multidisciplinary collaboration. Future studies need to identify the best instruments to measure physical activity in clinical practice. Future studies should focus on the effects of different types, time and intensity of PA in people with COPD and conduct randomized, adequately-powered, controlled trials to evaluate the long-term effectiveness of behavioral change interventions in PA.

Prevalence of Ureaplasma urealyticum, Chlamydia trachomatis, and Neisseria gonorrhoeae in gynecological outpatients, Taizhou, China.

OBJECTIVES: Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) are highly prevalent worldwide and may lead to some genital diseases. The objective of this large-scale study was to estimate the prevalence characteristics of UU, CT, and NG among women in Taizhou, Zhejiang Province, China. METHODS: A total of 13 303 women who visited the gynecologic outpatient service of Taizhou First People's Hospital in Taizhou from 2013 to 2018 were analyzed. The testing of UU, CT, and NG was performed on the collected vaginal swabs using real-time fluorescence quantitative polymerase chain reaction (RT-PCR) method. RESULTS: The overall infection rates of UU, CT, and NG were 62.04%, 10.20%, and 4.09% in the Taizhou-based population, respectively. The age-specific prevalence showed that younger women (age <25 years) were the preferred period for the positive detection of UU or CT, while elder women (age ≥40 years) had the highest prevalence of NG. In addition, the UU-CT co-infection pattern (7.32%) predominated in the study population, and CT was significantly associated with UU and NG. CONCLUSIONS: Our novel data demonstrated that UU, CT, and NG infection are prevalent among women in Taizhou, and comprehensive UU, CT, and NG screening guidelines and treatment policies for this population are warranted.

As-CATH1-6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses.

Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1-6) were identified and characterized from the endangered Chinese alligator (Alligator sinensis). As-CATH1-6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1-3 adopt a random coil secondary conformation, whereas As-CATH4-6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4-6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4-6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2-6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1-6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1-6 partially reveal the powerful immune system of the Chinese alligator.

Express Sequence Tag Analysis - Identification of Anseriformes Trypsin Genes from Full-Length cDNA Library of the Duck (Anas platyrhynchos) and Characterization of Their Structure and Function.

Trypsins are key proteins important in animal protein digestion by breaking down the peptide bonds on the carboxyl side of lysine and arginine residues, hence it has been used widely in various biotechnological processes. In the current study, a full-length cDNA library with capacity of 5·10(5) CFU/ml from the duck (Anas platyrhynchos) was constructed. Using express sequence tag (EST) sequencing, genes coding two trypsins were identified and two full-length trypsin cDNAs were then obtained by rapid-amplification of cDNA end (RACE)-PCR. Using Blast, they were classified into the trypsin I and II subfamilies, but both encoded a signal peptide, an activation peptide, and a 223-a.a. mature protein located in the C-terminus. The two deduced mature proteins were designated as trypsin-IAP and trypsin-IIAP, and their theoretical isoelectric points (pI) and molecular weights (MW) were 7.99/23466.4 Da and 4.65/24066.0 Da, respectively. Molecular characterizations of genes were further performed by detailed bioinformatics analysis. Phylogenetic analysis revealed that trypsin-IIAP has an evolution pattern distinct from trypsin-IAP, suggesting its evolutionary advantage. Then the duck trypsin-IIAP was expressed in an Escherichia coli system, and its kinetic parameters were measured. The three dimensional structures of trypsin-IAP and trypsin-IIAP were predicted by homology modeling, and the conserved residues required for functionality were identified. Two loops controlling the specificity of the trypsin and the substrate-binding pocket represented in the model are almost identical in primary sequences and backbone tertiary structures of the trypsin families.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Among older adults, type 2 diabetes mellitus (T2DM) is widely recognized as one of the most prevalent diseases. Diabetic nephropathy (DN) is a frequent complication of DM, mainly characterized by renal microvascular damage. Early detection, aggressive prevention, and cure of DN are key to improving prognosis. Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis. AIM: To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model. METHODS: The clinical data of 210 patients diagnosed with T2DM and admitted to the First People's Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed. According to whether the patients had DN, they were divided into the DN group (complicated with DN) and the non-DN group (without DN). Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM. The data were randomly split into a training set (n = 147) and a test set (n = 63) in a 7:3 ratio using a random function. The training set was used to construct the nomogram, decision tree, and random forest models, and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity, specificity, accuracy, recall, precision, and area under the receiver operating characteristic curve. RESULTS: Among the 210 patients with T2DM, 74 (35.34%) had DN. The validation dataset showed that the accuracies of the nomogram, decision tree, and random forest models in predicting DN in patients with T2DM were 0.746, 0.714, and 0.730, respectively. The sensitivities were 0.710, 0.710, and 0.806, respectively; the specificities were 0.844, 0.875, and 0.844, respectively; the area under the receiver operating characteristic curve (AUC) of the patients were 0.811, 0.735, and 0.850, respectively. The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models (P < 0.05), whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant (P > 0.05). CONCLUSION: Among the three prediction models, random forest performs best and can help identify patients with T2DM at high risk of DN.

Creatine kinase mitochondrial 2 promotes the growth and progression of colorectal cancer via enhancing Warburg effect through lactate dehydrogenase B.

Background: Mitochondrial creatine kinase (MtCK) plays a pivotal role in cellular energy metabolism, exhibiting enhanced expression in various tumors, including colorectal cancer (CRC). Creatine kinase mitochondrial 2 (CKMT2) is a subtype of MtCK; however, its clinical significance, biological functions, and underlying molecular mechanisms in CRC remain elusive. Methods: We employed immunohistochemical staining to discern the expression of CKMT2 in CRC and adjacent nontumor tissues of patients. The correlation between CKMT2 levels and clinical pathological factors was assessed. Additionally, we evaluated the association between CKMT2 and the prognosis of CRC patients using Kaplan-Meier survival curves and Cox regression analysis. Meanwhile, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of CKMT2 in different CRC cell lines. Finally, we explored the biological functions and potential molecular mechanisms of CKMT2 in CRC cells through various techniques, including qRT-PCR, cell culture, cell transfection, western blot, Transwell chamber assays, flow cytometry, and co-immunoprecipitation. Results: We found that CKMT2 was significantly overexpressed in CRC tissues compared with adjacent nontumor tissues. The expression of CKMT2 is correlated with pathological types, tumor size, distant metastasis, and survival in CRC patients. Importantly, CKMT2 emerged as an independent prognostic factor through Cox regression analysis. Experimental downregulation of CKMT2 expression in CRC cell lines inhibited the migration and promoted apoptosis of these cells. Furthermore, we identified a novel role for CKMT2 in promoting aerobic glycolysis in CRC cells through interaction with lactate dehydrogenase B (LDHB). Conclusion: In this study, we found the elevated expression of CKMT2 in CRC, and it was a robust prognostic indicator in CRC patients. CKMT2 regulates glucose metabolism via amplifying the Warburg effect through interaction with LDHB, which promotes the growth and progression of CRC. These insights unveil a novel regulatory mechanism by which CKMT2 influences CRC and provide promising targets for future CRC therapeutic interventions.

Molecular cloning, sequence analysis and homology modeling of the first caudata amphibian antifreeze-like protein in axolotl (Ambystoma mexicanum).

Antifreeze proteins (AFPs) refer to a class of polypeptides that are produced by certain vertebrates, plants, fungi, and bacteria and which permit their survival in subzero environments. In this study, we report the molecular cloning, sequence analysis and three-dimensional structure of the axolotl antifreeze-like protein (AFLP) by homology modeling of the first caudate amphibian AFLP. We constructed a full-length spleen cDNA library of axolotl (Ambystoma mexicanum). An EST having highest similarity (∼42%) with freeze-responsive liver protein Li16 from Rana sylvatica was identified, and the full-length cDNA was subsequently obtained by RACE-PCR. The axolotl antifreeze-like protein sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 93 amino acids. The calculated molecular mass and the theoretical isoelectric point (pl) of this mature protein were 10128.6 Da and 8.97, respectively. The molecular characterization of this gene and its deduced protein were further performed by detailed bioinformatics analysis. The three-dimensional structure of current AFLP was predicted by homology modeling, and the conserved residues required for functionality were identified. The homology model constructed could be of use for effective drug design. This is the first report of an antifreeze-like protein identified from a caudate amphibian.

Molecular cloning, sequence analysis and phylogeny of first caudata g-type lysozyme in axolotl (Ambystoma mexicanum).

Lysozymes are key proteins that play important roles in innate immune defense in many animal phyla by breaking down the bacterial cell-walls. In this study, we report the molecular cloning, sequence analysis and phylogeny of the first caudate amphibian g-lysozyme: a full-length spleen cDNA library from axolotl (Ambystoma mexicanum). A goose-type (g-lysozyme) EST was identified and the full-length cDNA was obtained using RACE-PCR. The axolotl g-lysozyme sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 184 amino acids. The calculated molecular mass and the theoretical isoelectric point (pl) of this mature protein are 21523.0 Da and 4.37, respectively. Expression of g-lysozyme mRNA is predominantly found in skin, with lower levels in spleen, liver, muscle, and lung. Phylogenetic analysis revealed that caudate amphibian g-lysozyme had distinct evolution pattern for being juxtaposed with not only anura amphibian, but also with the fish, bird and mammal. Although the first complete cDNA sequence for caudate amphibian g-lysozyme is reported in the present study, clones encoding axolotl's other functional immune molecules in the full-length cDNA library will have to be further sequenced to gain insight into the fundamental aspects of antibacterial mechanisms in caudate.

[Therapeutic effects of muscovite on ulcerative colitis in rats].

OBJECTIVE: To explore the efficacy of muscovite on iodoacetamide -induced ulcerative colitis in rats and elucidate its possible mechanism. METHODS: Ulcerative colitis was induced in female Sprague-Dawley (SD) rats by an intracolonic injection of iodoacetamide. A total of 48 rats were divided randomly(by the method of random digits table) into 6 groups: control group, model group, low-dose muscovite group (360 mg/kg), high-dose muscovite group (720 mg/kg), 5-aminosalicylie acid (5-ASA) group and muscovite plus 5-ASA group (combined treatment), and each group had 8 rats. The body weight, disease activity index (DAI), macroscopic damage and microscopic score of rats in each group were subsequently evaluated after dosing for 7 days. The protein levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and myeloperoxidase (MPO) activity were detected by enzyme-linked immunosorbent assay(ELISA) while the activity of nuclear facor(NF)-κB was determined by immunohistochemistry.One way ANOVA and rank-sum test were used. RESULTS: After doing, body weight macroscopic damage, microscopic score, TNF-α concentration, MPO and NF-κB activity of rats in each group were all significantly correlated with the dose of muscovite (r = 0.573, -0.647, -0.569, -0.681, -0.811, -0.842, all P < 0.05). High-dose muscovite group had no significant difference with 5-ASA group in body weightt, DAI, macroscopic damage, microscopic score, IL-8 concentration, TNF-α concentration, MPO and NF-κB activities((166 ± 5) vs (167 ± 5) g, 0.33 (0.00, 1.17) vs 0.17 (0.00, 0.83), 2.50 (2.00, 4.00) vs 3.00 (2.00, 3.00), 3.00 (2.00, 3.00) vs 2.50 (2.00, 3.00), (109 ± 17) vs (111 ± 15) pg/ml, (166 ± 38) vs (155 ± 45) pg/ml, (52 ± 6) vs (49 ± 4) U/g, 7.39 ± 0.42 vs 7.41 ± 0.34, all P > 0.05). The MPO and NF-κB activities of combined treatment group were lower than those of 5-ASA group((40 ± 4) vs (49 ± 4) U/g, 4.67 ± 0.72 vs 7.41 ± 0.34, all P < 0.05). However, other indices showed no significant difference with 5-ASA group (all P > 0.05). CONCLUSIONS: Rectal administration of muscovite ameliorates colonic inflammation of iodoacetamide-induced colitis. Its underlying mechanism is probably due to the regulation of inflammatory response. Muscovite may be a potential therapeutic agent for treatment of ulcerative colitis.

Development of a behavior change intervention to improve physical activity in patients with COPD using the behavior change wheel: a non-randomized trial.

The aim of this study was to evaluate whether a theory-based behavior change intervention could promote changes in physical activity (PA) and sedentary behavior (SB) among patients with chronic obstructive pulmonary disease (COPD), as well as its effects on symptoms of dyspnea, lung function, exercise capacity, self-efficacy, and health-related quality of life (HRQoL). A quasi-experimental design and convenience sampling were adopted. A total of 92 patients with stable COPD were recruited from outpatient and inpatient centers of two hospitals in Zhejiang Province, China. Both the experimental and control groups received standard medical care provided in the hospital. The experimental group performed a PA program based on the behavior change wheel theory. Outcomes were measured at baseline (T0) and after 4 weeks (T1), 8 weeks (T2), and 12 weeks of the intervention (T3). The primary outcome was PA measured by the International Physical Activity Questionnaire (IPAQ). Secondary outcomes included SB measured by the IPAQ, dyspnea measured by the modified Medical Research Council (mMRC) questionnaire, exercise capacity assessed by 6-min walk distance (6MWD), self-efficacy measured by the Exercise Self-Regulatory Efficacy Scale (EX-SRES), and HRQoL measured by the COPD Assessment Test (CAT). In addition, we measured lung function using a spirometer at baseline and 12 weeks. Of the 89 patients included in this study, 64 were male (71.91%), with a mean age of 67.03 ± 6.15 years. At 12 weeks, the improvements in PA, SB, mMRC, 6MWD, EX-SRES and CAT were all statistically significant (P < 0.05) in the experimental group compared to the control group. Repeated measures analysis of variance showed that there were group effects and time effects on total PA, SB, mMRC, 6MWD, EX-SRES, and CAT in both groups (P < 0.001). However, there was no significant difference in pulmonary function between the two groups before and after intervention (P < 0.05). The PA program based on theory significantly increased PA levels, reduced sedentary time, enhanced exercise capacity and self-efficacy as well as HRQoL in patients with stable COPD. Due to the limited intervention time in this study, the pulmonary function of COPD patients may not be reversed in a short time, and the long-term effect of this program on the pulmonary function of patients needs to be further explored.Trial registration: Clinical Trials.gov (ChiCTR2200060590). Registered 05/06/2022.

Role of TLR4/MyD88 Signaling Pathway in the Occurrence and Development of Uremia-Induced Myocardial Hypertrophy and Possible Mechanism.

The morbidity and mortality of cardiovascular disease (CVD) are relatively high. Studies have shown that most patients with chronic kidney disease (CKD) die from cardiovascular complications. Clinically, the pathophysiological state in which heart disease and kidney disease are causal and influence each other is called cardiorenal syndrome (CRS). Myocardial hypertrophy is the key stage of the heart structure changing from reversible to irreversible. It is an important pathophysiological basis for heart failure. Therefore, this study intends to start with the end-stage uremic phase of CKD to construct an animal model of uremia in rats to study the relationship between uremia, TLR4/MyD88 signaling pathway, and myocardial hypertrophy. The results showed that the uremic rats showed slow weight gain and were thinner. At 12 weeks (w), the serum creatinine and urea nitrogen of the uremic rats increased, and the global hypertrophy index increased. Detecting the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (MyD88) in blood samples of rats, we found that the expression of TLR4 and MyD88 increased at 12 w in the uremia group; pathological observation showed that at 4 weeks of uremia model rats, renal tissue compensatory hypertrophy, renal fibrous membrane proliferation, renal parenchyma atrophy, a large number of fibrous proliferation and inflammatory cell infiltration in the interstitium, and protein casts in the renal tubules were observed. Myocardial cells were obviously hypertrophy and disordered. At 12 w, renal tubules were obviously expanded, the epithelium was flat, the brush border disappeared, and the interstitial fibrous connective tissue of the myocardial tissue was proliferated. The detection of TLR4 and MyD88 in kidney tissue and myocardial tissue revealed that the positive expression of TLR4 and MyD88 gradually increased over time. Therefore, the final result of the study is that uremia can gradually lead to myocardial hypertrophy and TLR4 and MyD88 are highly expressed in serum, kidney, and myocardial tissues of uremic rats, suggesting that TLR4 and MyD88 may be related to the degree of uremic disease and the myocardium caused by it. Hypertrophy is related.

Suppressive effects of gecko cathelicidin on biofilm formation and cariogenic virulence factors of Streptococcus mutans.

OBJECTIVE: The aims of this study were to investigate the effectivity of gecko cathelicidin Gj-CATH2 on biofilm formation and cariogenic virulence factors of S. mutans, and preliminary explore its function mechanisms. DESIGN: Minimum inhibitory concentration and bacterial killing kinetics assays were performed to assess the antimicrobial effect of Gj-CATH2.The influence of Gj-CATH2 on S. mutans biofilm formation was determined by crystal violet staining method and observed by SEM. The effects of Gj-CATH2 on exopolysaccharides (EPS) synthesis, bacterial aggregation, acidogenicity and aciduricity of S. mutans were also investigated. Quantitative real-time PCR was conducted to acquire the expression profile of related genes. RESULTS: Gj-CATH2 showed strong bactericidal and anti-biofilm effects on S. mutans. SEM confirmed the reduction of the dense structure in S. mutans biofilm in Gj-CATH2-treated groups. Gj-CATH2 significantly inhibited EPS synthesis, cell aggregation, acid production of S. mutans, but showed no influence on its acid proof. Furthermore, the expression of genes related to biofilm formation (gtfB/C/D, gbpB/D), quorum sensing system (luxS and comD/E) and acidogenicity (ldh) was significantly suppressed by Gj-CATH2. Gj-CATH2 also displayed advantageous resistance in human saliva and exhibited negligible toxicity against mammalian cells. CONCLUSIONS: Gj-CATH2 inhibited S. mutans biofilm formation by targeting the bacterial adhesion and the biofilm maturation stages. Gj-CATH2 significantly suppressed virulence factors production of S. mutans, resulting in decreased EPS synthesis and reduced acidogenicity of bacteria. These findings suggest Gj-CATH2 might be a promising agent for clinical application in prevention of dental caries.

Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.

Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.

Derivatives of gecko cathelicidin-related antioxidant peptide facilitate skin wound healing.

Cathelicidins are a class of gene-encoded multifunctional factors in host defence systems. They have recently attracted a great deal of attention as promising drug candidates. Cathelicidins are well studied in vertebrates, yet no studies have been reported concerning gecko cathelicidin. Recently, we identified a novel cathelicidin from Gekko japonicus, Gj-CATH3. Unlike most cathelicidins, Gj-CATH3 exhibits potent antioxidant activity in vitro. Unfortunately, slight toxicity and high synthesis cost restrict its application. Thus, we designed a series of Gj-CATH3 analogues for development of short peptides with improved cell selectivity. Functional analysis showed that two truncated peptides, Gj-CATH3-(38-42)-peptide and Gj-CATH3-(33-42)-peptide, exhibited excellent antioxidant activity against ABTS and DPPH free radicals. Further, cytotoxicity and hemolytic activities were observably lower compared to Gj-CATH3. Interestingly, both peptides also demonstrate significant wound healing properties in a mouse model with full-thickness skin wounds. The peptides induce HaCaT cell proliferation and prevent decreases in SOD activity and increases of MDA concentration in injured-skin tissue. This report is the first to address cathelicidin from reptilia that exhibit potent wound healing activity. Our research will enrich understanding of cathelicidin biological functions, and provide a theoretical basis for its clinical application.

Toxic effects of heavy metals and their accumulation in vegetables grown in a saline soil.

A pot experiment was carried out to evaluate the effects of heavy metals on biomass, chlorophyll, and antioxidative enzyme activities of eight vegetables grown in a saline soil. The heavy metal accumulation in vegetables was also investigated. Results show that biomass and chlorophyll content of crops decreased with the increase of heavy metal concentration while peroxidase activity increased at low concentration and decreased at high concentration. The total translocation factor values in the eight vegetables are in order: water spinach>Chinese kale>pakchoi>edible amaranth>leaf mustard>Chinese flowering cabbage>green capsicum>tomato. Tomato, which is the most salt tolerant crop of the eight vegetables, also is the most heavy metals resistant studied in terms of growth, peroxidase activity and heavy metals translocation. Salt tolerant fruit vegetables such as tomato might be potential crops for the safe use of saline soils polluted with heavy metals.

[Current progress in antimicrobial peptides against bacterial biofilms].

Microbial biofilm, a consortium of microbial cells protected by a self-produced polymer matrix, is considered as one main cause of current bacterial drug resistance. As a new type of antimicrobial agents, antimicrobial peptides provide a new strategy for the treatment of antibiotic resistant bacteria biofilm infections. Antimicrobial peptides have shown unique advantages in preventing microbial colonization of surfaces, killing bacteria in biofilms or disrupting the mature biofilm structure. This review systemically analyzes published data in the recent 30 years to summarize the possible anti-biofilm mechanisms of antimicrobial peptides. We hope that this review can provide reference for the treatment of infectious diseases by pathogenic microbial biofilm.

Mining the potential prognostic value of synaptosomal-associated protein 25 (SNAP25) in colon cancer based on stromal-immune score.

BACKGROUND: Colon cancer is one of the deadliest tumors worldwide. Stromal cells and immune cells play important roles in cancer biology and microenvironment across different types of cancer. This study aimed to identify the prognostic value of stromal/immune cell-associated genes for colon cancer in The Cancer Genome Atlas (TCGA) database using bioinformatic technology. METHODS: The gene expression data and corresponding clinical information of colon cancer were downloaded from TCGA database. Stromal and immune scores were estimated based on the ESTIMATE algorithm. Sanger software was used to identify the differentially expressed genes (DEGs) and prognostic DEGs based on stromal and immune scores. External validation of prognostic biomarkers was conducted in Gene Expression Omnibus (GEO) database. Gene ontology (GO) analysis, pathway enrichment analysis, and gene set enrichment analysis (GSEA) were used for functional analysis. STRING and Cytoscape were used to assess the protein-protein interaction (PPI) network and screen hub genes. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of hub genes in clinical tissues. Synaptosomal-associated protein 25 (SNAP25) was selected for analyzing its correlations with tumor-immune system in the TISIDB database. RESULTS: Worse overall survivals of colon cancer patients were found in high stromal score group (2963 vs. 1930 days, log-rank test P = 0.038) and high immune score group (2894 vs. 2230 days, log-rank test P = 0.076). 563 up-regulated and 9 down-regulated genes were identified as stromal-immune score-related DEGs. 70 up-regulated DEGs associated with poor outcomes were identified by COX proportional hazard regression model, and 15 hub genes were selected later. Then, we verified aquaporin 4 (AQP4) and SNAP25 as prognostic biomarkers in GEO database. qRT-PCR results revealed that AQP4 and SNAP25 were significantly elevated in colon cancer tissues compared with adjacent normal tissues (P = 0.003, 0.001). GSEA and TISIDB suggested that SNAP25 involved in cancer-related signaling pathway, immunity and metabolism progresses. CONCLUSION: SNAP25 is a microenvironment-related and immune-related gene that can predict poor outcomes in colon cancer.

Knockdown of TUG1 by shRNA inhibited renal cell carcinoma formation by miR-299-3p/VEGF axis in vitro and in vivo.

Renal cell carcinoma (RCC) is one of the top ten deadly malignancies in the world. The long non-coding RNA taurine up-regulated gene 1 (TUG1) is a transcript that is up-regulated by taurine. There is ample evidence that TUG1 plays a crucial role in the progression of various cancers. This study aimed to investigate the role of TUG1 in RCC and its underlying molecular mechanisms. In the current study, knockdown of TUG1 by shRNA (sh-TUG1) significantly inhibited proliferation, invasion, migration and EMT processes of ACHN cells and OS-RC-2 cells, and induced apoptosis. Besides, bioinformatics analysis revealed that miR-299-3p is a target of TUG1. TUG1 overexpression (LV-TUG1) significantly inhibited the expression of miR-299-3p, whereas sh-TUG1 showed the opposite effect. Dual luciferase reporter assay further confirmed the targeting relationship between TUG1 and miR-299-3p. In addition, vascular endothelial growth factor (VEGFA) is a target of miR-299-3p. Knockdown of VEGFA (si-VEGFA) significantly inhibited the proliferation and motility of ACHN cells, and induced apoptosis. RT-qPCR results showed that sh-TUG1 similarly inhibited VEGFA expression. Further functional analysis indicated that sh-TUG1 inhibited tumorigenesis by down-regulating VEGFA levels. However, LV-TUG1 showed the opposite effects. Furthermore, animal experiments have shown that sh-TUG1 inhibited tumor growth and metastasis and induces apoptosis in vivo. These results indicate that sh-TUG1 inhibited renal cell carcinoma formation by miR-299-3p/VEGF axis in vitro and in vivo. Taken together, all of these results reveal a novel mechanism of TUG1 in RCC tumorigenesis, suggesting that targeted drugs for TUG1 provides a new direction for the treatment of RCC.