Progerin Inhibits the Proliferation and Migration of Melanoma Cells by Regulating the Expression of Paxillin.

Objective: Progerin, the underlying cause of Hutchinson-Gilford Progeria Syndrome (HGPS), has been extensively studied for its impact on normal cells and premature aging patients. However, there is a lack of research on its specific effects on tumor cells. Melanoma is one of the most common malignant tumors with high morbidity and mortality. This study aimed to elucidate the potential therapeutic role of progerin in melanoma. Materials and Methods: We constructed the melanoma A375 cell line and M14 cell line with stable expression of progerin. The expression of progerin, paxillin, and epithelial-mesenchymal transition (EMT) marker proteins in each cell group was measured using Western blot. The migration, proliferation, and cell cycle of cancer cells were assessed using the transwell assay, wound healing assay, colony formation assay, CCK 8 assay, and flow cytometry. RT-qPCR technology was used to examine the impact of progerin overexpression on microRNA expression. Finally, we transfected paxillin into the progerin overexpression cell group to verify whether progerin regulates the phenotype of tumor cells through paxillin. Results: Our study demonstrated that overexpression of progerin leads to decreased expression of paxillin and inhibits cancer cell migration, proliferation, EMT process and cell cycle progression. Additionally, rescue experiments revealed that the migration, proliferation ability, and EMT marker protein expression in progerin overexpressing cancer cells could be partially restored by transfecting a plasmid containing the paxillin gene. Mechanistic investigations further revealed that progerin achieves this inhibition of paxillin expression by upregulating miR-212. Conclusion: This study reveals that progerin may inhibit the migration and proliferation of melanoma cells through the miR-212/paxillin axis, which provides a new approach for the future treatment of this disease.

Factors associated with medial meniscal extrusion in non-osteoarthritic knees with medial meniscus tears: A cross-sectional study.

BACKGROUND: Medial meniscal extrusion (MME) plays an important role in the progression of knee osteoarthritis. Exploring the factors associated with MME in non-osteoarthritic knees may assist in the prevention of osteoarthritis. OBJECTIVE: To identify the factors associated with pathologic MME in non-osteoarthritic knees with medial meniscus tears (MMTs). DESIGN: A cross-sectional study. PARTICIPANTS: One hundred fifty patients with non-osteoarthritic knees who underwent arthroscopic surgery for MMT. Patients were divided into a pathologic MME group (n = 54) and a control group (n = 96) based on whether a pathologic MME was present on magnetic resonance (MR) images. SETTING: Tertiary medical institution. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The MME distance was measured on a coronal MR image obtained at the midpoint of the medial femoral condyle. An MME distance ≥3 mm was considered to indicate pathologic MME. Demographic and clinical data were collected as variables. Multivariable logistic regression analysis was performed to identify factors associated with pathologic MME. RESULTS: After multivariable adjustment, body mass index (BMI) and the type of MMT were associated significantly with pathologic MME in the multivariable logistic regression model. Each unit higher in BMI was associated with a 13% higher risk of pathologic MME (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.01-1.28, p = .04). The odds of pathologic MME were approximately four times and three times higher for radial tears (OR 4.34, 95% CI 1.25-15.03, p = .02) and complex tears (OR 3.07, 95% CI 1.17-8.05, p = .02) than for horizontal and longitudinal tears. CONCLUSIONS: BMI and the type of MMT were independent factors associated with pathologic MME in non-osteoarthritic knees with MMT. A higher BMI, radial tears, and complex tears were predisposed to pathologic MME.

The clinical value of serum-related indexes in differentiating simple premature thelarche from idiopathic central precocious puberty.

Objective: To explore the changes of serum-related indexes at different time points, so as to identify the critical time of converting from simple premature thelarche (PT) to idiopathic central precocious puberty (ICPP). Methods: This is a retrospective study. The subjects of the study were 50 girls with PT who were admitted to the Children's Hospital of Hebei Province from January 2019 to September 2020. The enrolled 50 children were divided into the conversion group(n=12) and the non-conversion group(n=38) according to whether PT was converted into ICPP during follow-up. Furthermore, the levels of serum-related indexes and uterine and ovarian volumes were compared after the diagnosis of PT. Results: The IGF-1 and IGFBP-3 levels of children in the conversion group began to change significantly from six months after the diagnosis, with statistically significant differences when compared with the levels of children at the initial diagnosis, three months and those of the non-conversion group at the same time points (p<0.05). The levels of vitamin-D, DHEA and leptin began to change significantly at nine months after the diagnosis (p<0.05). Besides, uterine and ovarian volumes in the conversion group began to increase significantly six months after the diagnosis, with statistically significant differences when compared with those in the non-conversion group (p<0.05). Conclusion: Findings in our study suggest that regular monitoring of vitamin-D, IGF-1, IGFBP-3, DHEA and leptin levels, and uterine and ovarian volumes can predict the conversion from PT to ICPP at an early stage.

Bufei Yishen formula protects the airway epithelial barrier and ameliorates COPD by enhancing autophagy through the Sirt1/AMPK/Foxo3 signaling pathway.

OBJECT: Bufei Yishen formula (BYF), a traditional Chinese medicine alleviates COPD symptoms and suppresses airway epithelial inflammation. In this study, we determined whether BYF protects the airway epithelial barrier from destruction in COPD rats. METHODS: The protective effects of BYF on the airway epithelial barrier were examined in a rat COPD model. BEAS-2B epithelial cells were exposed to cigarette smoke extract (CSE) to determine the effect of BYF on epithelial barrier function. Transcriptomic and network analyses were conducted to identify the protective mechanisms. RESULTS: Oral BYF reduced the severity of COPD in rats by suppressing the decline in lung function, pathological changes, inflammation, and protected airway epithelial barrier function by upregulating apical junction proteins, including occludin (OCLN), zonula occludens (ZO)-1, and E-cadherin (E-cad). BYF treatment reduced epithelial permeability, and increased TEER as well as the apical junction proteins, OCLN, ZO-1, and E-cad in BEAS-2B cells exposed to CSE. Furthermore, 58 compounds identified in BYF were used to predict 421 potential targets. In addition, the expression of 572 differentially expressed genes (DEGs) was identified in CSE-exposed BEAS-2B cells. A network analysis of the 421 targets and 572 DEGs revealed that BYF regulates multiple pathways, of which the Sirt1, AMPK, Foxo3, and autophagy pathways may be the most important with respect to protective mechanisms. Moreover, in vitro experiments confirmed that nobiletin, one of the active compounds in BYF, increased apical junction protein levels, including OCLN, ZO-1, and E-cad. It also increased LC3B and phosphorylated AMPK levels and decreased the phosphorylation of FoxO3a. CONCLUSIONS: BYF protects the airway epithelial barrier in COPD by enhancing autophagy through regulation of the SIRT1/AMPK/FOXO3 signaling pathway.

Low-dose venetoclax combined with azacitidine for blastic plasmacytoid dendritic cell neoplasm: a case report and literature review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that is highly aggressive with a poor prognosis. There is no standard treatment for BPDCN. Although conventional chemotherapies are usually sensitive in the initial therapy, relapse and drug resistance are inevitable within a short duration. Targeted therapies have enlightened new prospects for the treatment of BPDCN, especially for those in a frail state and intolerable to standard chemotherapies or hematopoietic stem cell transplantation. Here, we report an 82-year-old man diagnosed with cutaneous-limited BPDCN. Considering the old age and limited involvement of the tumor, we reduced the dosage of venetoclax. His skin lesions subsided significantly after 1 cycle of azacytidine (100 mg d1-7) combined with reduced doses of venetoclax (200 mg d1-14). The reduction in the dose of venetoclax avoided severe myelosuppression while achieving satisfactory outcomes. The patient received 2 cycles of therapy with no skin lesions re-occurred for 7 months before relapsing.

Effect of ATG8 or SAC1 deficiency on the cell proliferation and lifespan of the long-lived PMT1 deficiency yeast cells.

Autophagy is pivotal in maintaining intracellular homeostasis, which involves various biological processes, including cellular senescence and lifespan modulation. Being an important member of the protein O-mannosyltransferase (PMT) family of enzymes, Pmt1p deficiency can significantly extend the replicative lifespan (RLS) of yeast cells through an endoplasmic reticulum (ER) unfolded protein response (UPR) pathway, which is participated in protein homeostasis. Nevertheless, the mechanisms that Pmt1p regulates the lifespan of yeast cells still need to be explored. In this study, we found that the long-lived PMT1 deficiency strain (pmt1Δ) elevated the expression levels of most autophagy-related genes, the expression levels of total GFP-Atg8 fusion protein and free GFP protein compared with wild-type yeast strain (BY4742). Moreover, the long-lived pmt1Δ strain showed the greater dot-signal accumulation from GFP-Atg8 fusion protein in the vacuole lumen through a confocal microscope. However, deficiency of SAC1 or ATG8, two essential components of the autophagy process, decreased the cell proliferation ability of the long-lived pmt1Δ yeast cells, and prevented the lifespan extension. In addition, our findings demonstrated that overexpression of ATG8 had no potential effect on the RLS of the pmt1Δ yeast cells, and the maintained incubation of minimal synthetic medium lacking nitrogen (SD-N medium as starvation-induced autophagy) inhibited the cell proliferation ability of the pmt1Δ yeast cells with the culture time, and blocked the lifespan extension, especially in the SD-N medium cultured for 15 days. Our results suggest that the long-lived pmt1Δ strain enhances the basal autophagy activity, while deficiency of SAC1 or ATG8 decreases the cell proliferation ability and shortens the RLS of the long-lived pmt1Δ yeast cells. Moreover, the maintained starvation-induced autophagy impairs extension of the long-lived pmt1Δ yeast cells, and even leads to the cell death.

Targeting DDX11 promotes PARP inhibitor sensitivity in hepatocellular carcinoma by attenuating BRCA2-RAD51 mediated homologous recombination.

Homologous recombination (HR) is a major DNA double-strand break (DSB) repair pathway of clinical interest because of treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). Cooperation between RAD51 and BRCA2 is pivotal for DNA DSB repair, and its dysfunction induces HR deficiency and sensitizes cancer cells to PARPi. The depletion of the DEAD-box protein DDX11 was found to suppress HR in hepatocellular carcinoma (HCC) cells. The HR ability of HCC cells is not always dependent on the DDX11 level because of natural DDX11 mutations. In Huh7 cells, natural DDX11 mutations were detected, increasing the susceptibility of Huh7 cells to olaparib in vitro and in vivo. The HR deficiency of Huh7 cells was restored when CRISPR/Cas9-mediated knock-in genomic editing was used to revert the DDX11 Q238H mutation to wild type. The DDX11 Q238H mutation impeded the phosphorylation of DDX11 by ATM at serine 237, preventing the recruitment of RAD51 to damaged DNA sites by disrupting the interaction between RAD51 and BRCA2. Clinically, a high level of DDX11 correlated with advanced clinical characteristics and a poor prognosis and served as an independent risk factor for overall and disease-free survival in patients with HCC. We propose that HCC with a high level of wild-type DDX11 tends to be more resistant to PARPi because of enhanced recombination repair, and the key mutation of DDX11 (Q238H) is potentially exploitable.

Hyperlipidemia in immune thrombocytopenia: a retrospective study.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and bleeding manifestations. However, some patients also suffered from atherosclerosis or even infarction. Apart from activated platelets, lipid metabolism takes a large part in the formation of atherosclerosis and metabolic syndrome. The lipid metabolic state in ITP patients is still unknown. METHODS: We retrospectively reviewed 302 hospitalized ITP patients in our cohort, comparing their blood lipids, bleeding symptoms, metabolic diseases and treatment responses. RESULTS: We found a high proportion of ITP patients suffered from hyperlipidemia, and other metabolic diseases including cardiovascular or cerebral atherosclerosis or infarction, hypertension, and type 2 diabetes. Hyperlipidemia was associated with severe bleeding and treatment refractoriness in ITP. Statins could alleviate thrombocytopenia and bleeding severity, and facilitate ITP treatment, while improving hyperlipidemia in ITP patients. CONCLUSIONS: Our present study demonstrated that lipid metabolism might play an indispensable role in ITP pathogenesis and development.

Network Pharmacology-Based Approach to Investigate the Active Ingredients and Therapeutic Mechanisms of Jingu Tongxiao Pill against Osteoarthritis.

This study aimed to investigate the active ingredients and therapeutic mechanisms of Jingu Tongxiao Pill (JGTXP), a commonly used Chinese patent medicine, in treating osteoarthritis (OA) via network pharmacology analysis combined with experimental validation. First, we administered JGTXP to rat plasma and identified the candidate active compounds. Next, target prediction, protein-protein interaction, compound-target network construction, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for JGTXP. Lastly, the network-derived key targets and pathways were validated in vitro and in vivo. Finally, we identified 106 compounds in JGTXP and 24 absorbed compounds in the rat plasma. Network analysis revealed that JGTXP interferes with OA mainly via regulating the inflammatory response, collagen catabolic process, and osteoclast differentiation, and the nuclear factor kappa B (NF-κB) signaling pathway plays a pivotal role in these processes. Experimentally, JGTXP exerted potential protective effects on articular cartilage and inhibited expression of inflammatory mediators and collagen catabolism-related proteins, including interleukin 1 beta (IL-1ß), interleukin 6, tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase (MMP) 3 and MMP13, in a papain-induced OA rat model. Consistently, mRNA expression levels of these factors and nitric oxide release were suppressed by JGTXP in an LPS-induced RAW 264.7 inflammation model. The reporter gene assay showed that JGTXP could reduce the transcriptional activity of NF-κB. Consecutive western blot analysis demonstrated that nuclear NF-κB p65, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) expression were inhibited while cytoplasmic NF-κB p65 was upregulated by JGTXP. Using a combination of chemical profiling, network pharmacology analysis, and experimental validation, we preliminarily clarified the active ingredients of JGTXP intervention for OA and demonstrated that JGTXP ameliorates OA, at least partially, by regulating the NF-κB signaling pathway.

Ultra-sensitive electrochemiluminescent biosensor for miRNA based on CRISPR/Cas13a trans-cleavage-triggered hybridization chain reaction and magnetic-assisted enrichment.

The great selectivity and trans-cleavage activity of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a had been coupled with high amplification efficiency of hybridization chain reaction (HCR) and magnetic-assisted enrichment, high sensitivity of electrochemiluminescence (ECL) detection to develop an ultra-sensitive biosensor for microRNA-21 (miRNA-21). The CRISPR/Cas13a was used to recognize target RNA with high specificity and performed the trans-cleavage activity. An initiation strand was generated to bind to the probe on the surface of nanomagnetic beads and then trigged HCR to produce long double-strand DNAs (dsDNAs) to realize signal amplification. Ru(phen)32+ can be inserted in the groove of the dsDNAs and acts as the ECL indicator, which can be separated through magnetic enrichment and allowed the platform to reduce the signal background. Under the optimized conditions, there is a good linear correlation between the ECL intensity and the logarithm of miRNA-21 concentration in the range 1 fM-10 nM; the limit of detection (LOD) was 0.53 fM. The proposed system was applied to detect miRNA-21 from the urine of acute kidney injury (AKI) patients with good results.

Recent advances of artificial intelligence in melanoma clinical practice.

Skin melanoma is a lethal cancer. The incidence of melanoma is increasing rapidly in all regions of the world. Despite significant breakthroughs in melanoma treatment in recent years, precise diagnosis of melanoma is still a challenge in some cases. Even specialized physicians may need time and effort to make accurate judgments. As artificial intelligence (AI) technology advances into medical practice, it may bring new solutions to this problem based on its efficiency, accuracy, and speed. This paper summarizes the recent progress of AI in melanoma-related applications, including melanoma diagnosis and classification, the discovery of new medication, guiding treatment, and prognostic assessment. The paper also compares the effectiveness of various algorithms in melanoma application and suggests future research directions for AI in melanoma clinical practice.

Serum C reactive protein and procalcitonin are valuable predictors of coronary heart disease and poor prognosis in the elderly.

OBJECTIVES: To investigate the potential of serum C-reactive protein (CRP) and procalcitonin (PCT) for predicting coronary heart disease (CHD) in elderly patients, as well as their impact on prognosis. METHODS: This retrospective analysis included 120 elderly patients with CHD (CHD group) and 100 patients without cardiovascular disease (control group). CHD patients were followed up for 12 months after discharge. Patients with readmission due to adverse cardiovascular events were incorporated into a poor prognosis group, and the rest were considered a good prognosis group. Serum CRP and PCT were measured by Latex immunoturbidimetric assay and enzyme-linked fluorescent assay. RESULTS: Serum CRP and PCT levels in the CHD group were considerably higher than those in the control group. Serum CRP and PCT were found to be predictive factors for CHD by logistic regression study, and the area under the curve (AUC) of the combination examination of CRP and PCT was greater than that of CRP or PCT alone, suggesting that the combination was most valuable for the prediction of CHD in the elderly. Furthermore, the levels of CRP and PCT in the poor prognosis group were substantially higher than those in the good prognosis group. Logistic regression found that serum CRP and PCT were independent factors affecting the prognosis of CHD. The AUR of the combined examination of CRP and PCT was greater than that of the CRP or PCT alone, suggesting that the combination had a better prognostic value. CONCLUSIONS: Serum PCT and CRP levels are abnormally elevated in elderly patients with CHD, and higher levels of PCT and CRP are associated with higher risk of CHD and poor prognosis. The determination of PCT and CRP is of great significance in guiding clinical treatment.

Vemurafenib induces a noncanonical senescence-associated secretory phenotype in melanoma cells which promotes vemurafenib resistance.

More than one half melanoma patients have BRAF gene mutation. BRAF inhibitor vemurafenib is an effective medication for these patients. However, acquired resistance is generally inevitable, the mechanisms of which are not fully understood. Cell senescence and senescence-associated secretory phenotype (SASP) are involved in extensive biological functions. This study was designed to explore the possible role of senescent cells in vemurafenib resistance. The results showed that vemurafenib treatment induced BRAF-mutant but not wild-type melanoma cells into senescence, as manifested by positive ß-galactosidase staining, cell cycle arrest, enlarged cellular morphology, and cyclin D1/p-Rb pathway inhibition. However, the senescent cells induced by vemurafenib (SenV) did not display DNA damage response, p53/p21 pathway activation, reactive oxygen species accumulation, decline of mitochondrial membrane potential, or secretion of canonical SASP cytokines. Instead, SenV released other cytokines, including CCL2, TIMP2, and NGFR, to protect normal melanoma cells from growth inhibition upon vemurafenib treatment. Xenograft experiments further confirmed that vemurafenib induced melanoma cells into senescence in vivo. The results suggest that vemurafenib can induce robust senescence in BRAFV600E melanoma cells, leading to the release of resistance-conferring cytokines. Both the senescent cells and the resistant cytokines could be potential targets for tackling vemurafenib resistance.

Differentiation in TCM patterns of chronic obstructive pulmonary disease by comprehensive metabolomic and lipidomic characterization.

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex disease involving inflammation, cell senescence, and autoimmunity. Dialectical treatment for COPD with traditional Chinese medicine (TCM) has the advantage of fewer side effects, more effective suppression of inflammation, and improved immune function. However, the biological base of TCM pattern differentiation in COPD remains unclear. Methods: Liquid Chromatography-Quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap MS/MS) based metabolomics and lipidomics were used to analyze the serum samples from COPD patients of three TCM patterns in Lung Qi Deficiency (n=65), Lung-Kidney Qi Deficiency (n=54), Lung-Spleen Qi Deficiency (n=52), and healthy subjects (n=41). Three cross-comparisons were performed to characterize metabolic markers for different TCM patterns of COPD vs healthy subjects. Results: We identified 28, 8, and 16 metabolites with differential abundance between three TCM patterns of COPD vs healthy subjects, respectively, the metabolic markers included cortisol, hypoxanthine, fatty acids, alkyl-/alkenyl-substituted phosphatidylethanolamine, and phosphatidylcholine, etc. Three panels of metabolic biomarkers specific to the above three TCM patterns yielded areas under the receiver operating characteristic curve of 0.992, 0.881, and 0.928, respectively, with sensitivity of 97.1%, 88.6%, and 91.4%, respectively, and specificity of 96.4%, 81.8%, and 83.9%, respectively. Discussion: Combining metabolomics and lipidomics can more comprehensively and accurately trace metabolic markers. As a result, the differences in metabolism were proven to underlie different TCM patterns of COPD, which provided evidence to aid our understanding of the biological basis of dialectical treatment, and can also serve as biomarkers for more accurate diagnosis.

Effects of multi-organ crosstalk on the physiology and pathology of adipose tissue.

In previous studies, adipocytes were found to play an important role in regulating whole-body nutrition and energy balance, and are also important in energy metabolism, hormone secretion, and immune regulation. Different adipocytes have different contributions to the body, with white adipocytes primarily storing energy and brown adipocytes producing heat. Recently discovered beige adipocytes, which have characteristics in between white and brown adipocytes, also have the potential to produce heat. Adipocytes interact with other cells in the microenvironment to promote blood vessel growth and immune and neural network interactions. Adipose tissue plays an important role in obesity, metabolic syndrome, and type 2 diabetes. Dysfunction in adipose tissue endocrine and immune regulation can cause and promote the occurrence and development of related diseases. Adipose tissue can also secrete multiple cytokines, which can interact with organs; however, previous studies have not comprehensively summarized the interaction between adipose tissue and other organs. This article reviews the effect of multi-organ crosstalk on the physiology and pathology of adipose tissue, including interactions between the central nervous system, heart, liver, skeletal muscle, and intestines, as well as the mechanisms of adipose tissue in the development of various diseases and its role in disease treatment. It emphasizes the importance of a deeper understanding of these mechanisms for the prevention and treatment of related diseases. Determining these mechanisms has enormous potential for identifying new targets for treating diabetes, metabolic disorders, and cardiovascular diseases.

Yangqing Chenfei formula alleviates silica-induced pulmonary inflammation in rats by inhibiting macrophage M1 polarization.

BACKGROUND: Yangqing Chenfei formula (YCF) is a traditional Chinese medicine formula for early-stage silicosis. However, the therapeutic mechanism is unclear. The purpose of this study was to determine the mechanism for the effects of YCF on early-stage experimental silicosis. METHODS: The anti-inflammatory and anti-fibrotic effects of YCF were determined in a silicosis rat model, which was established by intratracheal instillation of silica. The anti-inflammatory efficacy and molecular mechanisms of YCF were examined in a lipopolysaccharide (LPS)/interferon (IFN)-γ-induced macrophage inflammation model. Network pharmacology and transcriptomics were integrated to analyze the active components, corresponding targets, and anti-inflammatory mechanisms of YCF, and these mechanisms were validated in vitro. RESULTS: Oral administration of YCF attenuated the pathological changes, reduced inflammatory cell infiltration, inhibited collagen deposition, decreased the levels of inflammatory factors, and reduced the number of M1 macrophages in the lung tissue of rats with silicosis. YCF5, the effective fraction of YCF, significantly attenuated the inflammatory factors induced by LPS and IFN-γ in M1 macrophages. Network pharmacology analysis showed that YCF contained 185 active components and 988 protein targets, which were mainly associated with inflammation-related signaling pathways. Transcriptomic analysis showed that YCF regulated 117 reversal genes mainly associated with the inflammatory response. Integrative analysis of network pharmacology and transcriptomics indicated that YCF suppressed M1 macrophage-mediated inflammation by regulating signaling networks, including the mTOR, mitogen-activated protein kinases (MAPK), PI3K-Akt, NF-κB, and JAK-STAT signaling pathways. In vitro studies confirmed that the active components of YCF significantly decreased the levels of p-mTORC1, p-P38, and p-P65 by suppressing the activation of related-pathways. CONCLUSION: YCF significantly attenuated the inflammatory response in rats with silicosis via the suppression of macrophage M1 polarization by inhibiting a "multicomponent-multitarget-multipathway" network.

The Distribution, Drug Susceptibility, and Dynamic Trends of Pseudomonas aeruginosa Infection in a Tertiary Hospital in China During 2016‒2022.

Background: Drug-resistant Pseudomonas aeruginosa infections rapidly increased and contributed to life-threatening nosocomial infections; however, the distribution, species, drug susceptibility and dynamic trends of P. aeruginosa infection in China remained unclear. This study was conducted to better understand the epidemiological data of increased P. aeruginosa infections from 2016 to 2022 in a hospital in China. Methods: This study involved 3301 patients infected with P. aeruginosa, diagnosed using a nosocomial infection surveillance system in a tertiary hospital between 2016 and 2022. The P. aeruginosa infections from 2016 to 2022 were assessed according to the hospital department and species, and the drug susceptibility was evaluated using 16 antimicrobial agents. Results: The P. aeruginosa infection prevalence in the hospital department was: Neurosurgery (14.30%), Emergency (13.30%), and Critical Care Medicine (11.69%). Samples for P. aeruginosa infection identification were from sputum (72.52%) and other secreta (9.91%). The P. aeruginosa infections demonstrated a greater sensitivity to amikacin (AMK, 91.82%), tobramycin (TOB, 82.79%), and gentamycin (GEN, 82.01%); however, P. aeruginosa infection demonstrated greater resistance to ticarcillin (22.57%), levofloxacin (21.63%), and ciprofloxacin (18.00%). Conclusion: The P. aeruginosa infections were commonly observed in the Neurosurgery, Emergency, and Critical Care Medicine departments and demonstrated greater sensitivity to AMK, TOB, and GEN than the other drugs.

Uncovering mechanisms of Baojin Chenfei formula treatment for silicosis by inhibiting inflammation and fibrosis based on serum pharmacochemistry and network analysis.

BACKGROUND: Baojin Chenfei formula (BCF), a Chinese herbal formula, has significant effects on improving the clinical symptoms of patients with silicosis. However, its active compounds and the underlying mechanisms have not yet fully been elucidated. PURPOSE: This study aimed to explore the underlying mechanisms of BCF in treating silicosis. METHODS: The rat model of silicosis was developed via a single intratracheal instillation of SiO2 suspension to examine the therapeutic impacts of BCF on silicosis. Subsequently, the active compounds, targets, and mechanisms of BCF were analyzed based on serum pharmacochemistry and network analysis. Finally, the underlying mechanisms of representative compounds of BCF were validated in vitro experiments. RESULTS: BCF significantly alleviated SiO2-induced silicosis in rats, evidenced by improved lung function, decreased pathological injury, and reduced inflammatory response and fibrosis. 19 active compounds were identified from the rat serum samples after BCF gavage. Subsequently, 299 targets for these 19 compounds in BCF and 257 genes related to silicosis were collected. 26 overlapping targets, including AKT1, TNF, IL6, MAPK3, EGFR, and others, were obtained from the intersection of the 299 BCF-related targets and 257 silicosis-associated genes. These overlapping targets mainly corresponded to glycyrrhetic acid and paeoniflorin and were mainly associated with positive regulation of smooth muscle cell proliferation, positive regulation of MAP kinase activity, and inflammatory response. In vitro experiments also demonstrated that the representative compounds of BCF (glycyrrhetic acid and paeoniflorin) could suppress inflammatory response by the MAPK pathway, and also inhibited fibroblast activation by the EGFR-PI3K-AKT pathway. CONCLUSION: Active compounds of BCF, such as glycyrrhetic acid and paeoniflorin, could suppress inflammatory response by the MAPK pathway and suppress fibroblast activation by the EGFR-PI3K-AKT pathway. These might be the mechanisms of BCF in treating silicosis.

The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy.

Paxillin is a multi-domain adaptor protein. As an important member of focal adhesion (FA) and a participant in regulating cell movement, paxillin plays an important role in physiological processes such as nervous system development, embryonic development, and vascular development. However, increasing evidence suggests that paxillin is aberrantly expressed in many cancers. Many scholars have also recognized that the abnormal expression of paxillin is related to the prognosis, metastases, invasion, survival, angiogenesis, and other aspects of malignant tumors, suggesting that paxillin may be a potential cancer therapeutic target. Therefore, the study of how aberrant paxillin expression affects the process of tumorigenesis and metastasis will help to develop more efficacious antitumor drugs. Herein, we review the structure of paxillin and its function and expression in tumors, paying special attention to the multifaceted effects of paxillin on tumors, the mechanism of tumorigenesis and progression, and its potential role in tumor therapy. We also hope to provide a reference for the clinical prognosis and development of new tumor therapeutic targets.