Protein phosphatase 4 mediates palmitic acid-induced endothelial dysfunction by decreasing eNOS phosphorylation at serine 633 in HUVECs.

Plasma saturated free fatty acid (FFA)-induced endothelial dysfunction (ED) contributes to the pathogenesis of atherosclerosis and cardiovascular diseases. However, the mechanism underlying saturated FFA-induced ED remains unclear. This study demonstrated that palmitic acid (PA) induced ED by activating the NADPH oxidase (NOX)/ROS signaling pathway to activate protein phosphatase 4 (PP4) and protein phosphatase 2A (PP2A), thereby reducing endothelial nitric oxide synthase (eNOS) phosphorylation at Ser633 and Ser1177, respectively. Okadaic acid (OA) and fostriecin (FST), which are inhibitors of PP2A, inhibited the PA-induced decreases in eNOS phosphorylation at Ser633 and Ser1177. The antioxidants N-acetylcysteine (NAC) and apocynin (APO) or knockdown of gp91phox or p67phox (NOX subunits) restored PA-mediated downregulation of PP4R2 protein expression and eNOS Ser633 phosphorylation. Knockdown of the PP4 catalytic subunit (PP4c) specifically increased eNOS Ser633 phosphorylation, while silencing the PP2A catalytic subunit (PP2Ac) restored only eNOS Ser1177 phosphorylation. Furthermore, PA dramatically decreased the protein expression of the PP4 regulatory subunit R2 (PP4R2) but not the other regulatory subunits. PP4R2 overexpression increased eNOS Ser633 phosphorylation, nitric oxide (NO) production, cell migration and tube formation but did not change eNOS Ser1177 phosphorylation levels. Coimmunoprecipitation (Co-IP) suggested that PP4R2 and PP4c interacted with the PP4R3α and eNOS proteins. In summary, PA decreases PP4R2 protein expression through the Nox/ROS pathway to activate PP4, which contributes to ED by dephosphorylating eNOS at Ser633. The results of this study suggest that PP4 is a novel therapeutic target for ED and ED-associated vascular diseases.

The Antiangiogenic and Antitumor Effects of Scoparasin B in Non-Small-Cell Lung Cancer.

Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly target endothelial cell-mediated angiogenesis, ignoring tumor-cell-mediated VM and frequently leading to tumor recurrence and metastasis. Thus, development of bioactive molecules interfering with both tumor angiogenesis and VM is necessary. Identifying novel angiogenesis inhibitors from natural products is a promising strategy. Scoparasin B, a pimarane diterpene extracted from a marine-derived fungus, Eutypella sp. F0219, has an antibacterial effect. However, its effect on angiogenesis and VM remains unexplored. In this study, we first certified that scoparasin B showed a strong inhibition effect on angiogenesis and the VM process in vitro and ex vivo. Moreover, scoparasin B prominently impeded tumor growth, angiogenesis, and VM in an NCI-H1299 xenograft model. Further study revealed that scoparasin B restrained tumor angiogenesis and VM by reducing the VEGF-A level and suppressing the VEGF-A/VEGFR2 signaling pathway. This study first demonstrated scoparasin B inhibited tumor angiogenesis, VM, and tumor growth of NSCLC and revealed its underlying mechanism. These new findings further support the potential of scoparasin B as a novel angiogenesis inhibitor and give a hint for further exploring potential angiogenesis inhibitors from natural products.

Pediatric tinea capitis in Jilin Province: analyzing previous results from a new perspective.

OBJECTIVES: To investigate the current etiological, diagnostic, and therapeutic characteristics of tinea capitis in children in Jilin Province. METHODS: Sixty pediatric patients with tinea capitis were enrolled between August 2020 and December 2021. Data on calcofluor white (CFW) fluorescence microscopy, fungal culture, Wood's lamp examination, dermoscopy, treatment, and follow-up were collected and analyzed. RESULTS: 1. Of all the enrolled patients, 48 had a history of animal contact, mostly with cats and dogs. Fifty-one strains were isolated, of which 46 were Microsporum canis (M. canis). 2. All enrolled patients were examined using fluorescence microscopy, and 59 were positive. Forty-one cases of tinea alba were examined using Wood's lamp, and 38 were positive. Forty-two cases of tinea alba were examined using dermoscopy, and 39 demonstrated specific signs. Effective treatment manifested as a fading bright green fluorescence, decreased mycelial/spore load, reduced specific dermoscopic signs, and hair regrowth. 3. Treatment was terminated in 23 and 37 cases based on mycological and clinical cures, respectively. No recurrence occurred during follow-up. CONCLUSION: 1. M. canis is the predominant pathogen causing tinea capitis in children in Jilin Province. Animal contact is considered the main risk factor. 2. CFW fluorescence microscopy, Wood's lamp, and dermoscopy can be used to diagnose ringworms and follow-up patients. 3. Both mycological and clinical cures can be the endpoint of adequate treatment for tinea capitis.

Effect of Time Outdoors and Near-viewing Time on Myopia Progression in 9- to 11-year-old Children in Chongqing.

SIGNIFICANCE: We used an Akeso device to record the visual behavior of children with myopia in two learning modes. We found that online class mode may increase near-viewing time and reduce outdoor time compared with the traditional school mode and may be responsible for accelerating myopia progression. PURPOSE: We aimed to explore the effects of visual behavior in different learning modes on myopia progression among children 9 to 11 years old. METHODS: Forty-nine children were included and requested to use a wearable device to objectively record visual behavior in real time from November 2019 to November 2020; participants took online classes from mid-February to early May 2020 during this period. Data (including glasses-wearing time, outdoor time, and near-viewing time) were collected during two 14-day periods, which included the online class learning mode (March 2 to 15, 2020) and the traditional school mode (May 20 to June 2, 2020). Spherical equivalent refraction and axial length were obtained at baseline, at 6-month intervals, and 1 year later. RESULTS: Outdoor time during online class mode (median, 9.5 minutes; interquartile range, 0.75 to 48 minutes) was significantly lower than during the school mode (median, 29 minutes; interquartile range, 11.50 to 50 minutes; P < .001). The mean ± standard deviation of near-viewing time was significantly different between online class mode (396.58 ± 114.41 minutes) and school mode (376.52 ± 93.99 minutes; P = .007, F = 19.56). In comparison with the baseline examination (-2.33 ± 0.81 D), mean spherical equivalent refraction in oculus dexter corresponding to the 6-month examination was decreased (-2.94 ± 0.83 D, P = .001), indicating a significant increase in myopia during online class mode. CONCLUSIONS: This study provides evidence of the association of learning mode and myopia progression. Accelerated progression of myopia in online class mode may be related to increased near-viewing time and decreased time spent in outdoor activities.

A Potential Research Target for Scleral Remodeling: Effect of MiR-29a on Scleral Fibroblasts.

INTRODUCTION: The purpose of this study was to determine whether miR-29a regulates cell survival and apoptosis and the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), MMP-2, and collagen I in scleral fibroblasts. METHODS: We transfected scleral fibroblasts with the miR-29a mimic and inhibitor. The effects of miR-29a on cell proliferation and apoptosis were determined using the CCK-8 assay and flow cytometry, respectively. Quantitative polymerase chain reaction (qPCR) was used to determine whether miR-29a regulates the mRNA levels of PTEN, MMP-2, and collagen I. The protein expression of PTEN, MMP-2, and collagen I was also assessed by western blot analysis. RESULTS: The results of CCK-8 showed that, at 0, 24, 48, and 72 h after transfection, the relative optical density values in the mimic group were 0.233 ± 0.005, 0.380 ± 0.008, 0.650 ± 0.040, and 0.906 ± 0.032, and in the inhibitor group were 0.272 ± 0.011, 0.393 ± 0.029, 0.597 ± 0.059, and 0.950 ± 0.101, respectively. The flow cytometry results showed that the apoptosis rates of each group were as follows: the mimic group (0.043 ± 0.007), the NC group (0.040 ± 0.006), the inhibitor group (0.032 ± 0.003), the inhibitor NC group (0.027 ± 0.010), the lipofectamine group (0.027 ± 0.005), and the blank group (0.031 ± 0.009). The qPCR results indicated that in the mimic group, PTEN (0.795 ± 0.182, p = 0.2783), MMP-2 (0.621 ± 0.105, p = 0.0033), and COL1A1 (0.271 ± 0.100, p = 0.0002) expression decreased, whereas in the inhibitor group, PTEN (1.211 ± 0.100, p = 0.2614), MMP-2 (1.161 ± 0.053, p = 0.1190), and COL1A1 (1.7040 ± 0.093, p = 0.0003) increased. Western blot analysis showed that in the mimic group, the expression of PTEN (0.392 ± 0.039, p < 0.0001), MMP-2 (0.577 ± 0.017, p < 0.0001), and COL1A1 (0.072 ± 0.006, p < 0.0001) protein decreased, whereas in the inhibitor group, PTEN (1.043 ± 0.042, p = 0.9413), MMP-2 (1.397 ± 0.075, p = 0.0002), and COL1A1 (1.935 ± 0.081, p < 0.0001) expression increased. CONCLUSION: MiR-29a inhibits the expression of PTEN, MMP-2, and collagen I on scleral fibroblasts, which may provide a basis studies in sclera.

Characterization and Phylogenetic Analysis of the Mitochondrial Genome Sequence of Nisia fuliginosa (Hemiptera: Fulgoroidea: Meenoplidae).

We explored characterization of the mitochondrial genome (mitogenome or mtGenome) and phylogenetic analysis between 32 Fulgoroid species by sequencing and analyzing the mitogenome of Nisia fuliginosa Yang and Hu, 1985 (Hemiptera: Fulgoroidea: Meenoplidae), thereby making it the first determined mitogenome from the family Meenoplidae. The mitogenome was found to be 15,754 bp in length and contained 13 protein-coding genes (PCGs), 22 tRNA genes, two ribosomal RNA genes (rRNAs), and a control region. All PCGs started with typical ATN codons, except for nad1, which used GTG as the start codon. Canonical TAA termination codons were found in 10 PCGs and the remaining three genes (cox2, nad6, and nad1) had incomplete stop codons T. All tRNAs could fold into typical cloverleaf secondary structures, with the exception of trnC, trnV, and trnS1. Additionally, we compared the AT and GC skews of 13 PCGs of 32 Fulgoroidea mitogenomes, on the L-strand, the AT and GC skews were negative and positive, respectively. However, on the H-strand, the AT skew could be positive or negative and the GC skew was always negative. Phylogenetic results showed that the eight families of Fulgoroidea were divided into two large groups. Delphacidae formed a monophyletic group sister to a clade comprising Meenoplidae and other six families (Fulgoridae, Ricaniidae, Flatidae, Issidae, Caliscelidae, and Achilidae). Meenoplidae was located near the clade of Delphacidae, and Fulgoridae was located near the clade of Meenoplidae. Furthermore, Caliscelidae, Issidae, Ricaniidae, and Flatidae are closely related and they collectively formed a sister group to Achilidae.

Molecular mechanism of azoles resistant Candida albicans in a patient with chronic mucocutaneous candidiasis.

BACKGROUND: More and more azole-resistant strains emerged through the development of acquired resistance and an epidemiological shift towards inherently less susceptible species. The mechanisms of azoles resistance of Candida albicans is very complicated. In this study, we aim to investigate the mechanism of azole-resistant C. albicans isolated from the oral cavity of a patient with chronic mucocutaneous candidiasis (CMC). CASE PRESENTATION: CMC diagnosis was given based on clinical manifestations, laboratory test findings and gene sequencing technique. Minimum inhibitory concentration (MIC) of the fungal isolate, obtained from oral cavity termed as CA-R, was obtained by in vitro anti-fungal drugs susceptibility test. To further investigate the resistant mechanisms, we verified the mutations of drug target genes (i.e. ERG11 and ERG3) by Sanger sequencing, and verified the over-expression of ERG11 and drug efflux genes (i.e. CDR1 and CDR2) by RT-PCR. A heterozygous mutation of c.1162A > G resulting in p.K388E was detected in STAT1 of the patient. The expression of CDR1 and CDR2 in CA-R was 4.28-fold and 5.25-fold higher than that of type strain SC5314, respectively. CONCLUSIONS: Up-regulation of CDR1 and CDR2 was mainly responsible for the resistance of CA-R. For CMC or other immunodeficiency patients, drug resistance monitoring is necessary.

Roles of eNOS in atherosclerosis treatment.

BACKGROUND: Atherosclerosis (AS) is the main pathogeny of coronary heart disease, cerebral infarction and peripheral vascular disease. Endothelial dysfunction is one of the important pathogenesis of AS. As an important endothelium-derived relaxation factor, nitric oxide (NO) plays a role in cardiovascular protection and anti-AS function; but in the pathological state, endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS. This review summarized the research progresses in the treatment strategies for AS based on correcting the disordered eNOS/ NO signaling pathway. MAIN BODY: According to the topic, select the search terms 'atherosclerosis,' 'nitric oxide,' 'eNOS,' 'treatment,' 'management,' 'medication,' 'maintenance,' 'remission'. Using these terms, a structured literature search via multiple electronic databases was performed for the most recent trial evidence in recent years. We read and analyze these literatures carefully, classified these literatures according to their content, and then summarized and outlined the common main points in these classified literatures. Finally, literature data were organized to discuss these main points logically. We found that both aberrant expression and dysfunction of eNOS are closely related to AS development, and some new treatment strategies aimed at eNOS have been proposed, including upregulation of eNOS expression and inhibition of eNOS uncoupling. The former one is mainly related to inflammatory inhibition and protection of the PKB-eNOS signaling pathway; whereas the latter one is associated with the addition of the L-arginine substrate of eNOS, arginase inhibition, and the supplement of tetrahydrobiopterin, which can elevate no level. CONCLUSIONS: eNOS can be an important target for prevention and treatment of AS, and eNOS drugs may be another potent class of effective therapeutic treatment for AS following traditional lipid-lowering, anti-platelet, vasodilator drugs. But applying these experimental results to clinic treatment still requires further studies and development of biotechnology.

Simultaneous dermatophytosis and keratomycosis caused by Trichophyton interdigitale infection: a case report and literature review.

BACKGROUND: Dermatophytosis is a fungal infectious disease caused by dermatophytes, which produce protease and keratinase to digest keratin, leading to the colonization, invasion, and infection of the stratum corneum of the skin, hair shafts, and nails. Trichophyton interdigitale belongs to Trichophyton mentagrophytes complex, which is the common pathogen causing dermatophytosis. Fungal keratitis, also called keratomycosis, is an infectious disease of cornea. CASE PRESENTATION: Here, we report a case of simultaneous dermatophytosis and keratomycosis caused by Trichophyton interdigitale. A 67-year-old man presented with extensive erythema all over the body since 4 years ago, fungal infection of left eye for 2 years, and loss of vision in the eye. These symptoms had become aggravated in the last month. Dermatological examinations showed extensive erythematous plaques with clear borders and scales, scattered red papules with ulceration, and scabs throughout the body. Onychomycosis was observed on the nails of left hand, conjunctival infection with secretion and loss of vision were noted in left eye. Hyaline septate hyphae were observed under direct microscopic examination, fungal culture and internal transcribed spacer sequencing revealed T. interdigitale. Histopathological examination suggested infectious granuloma. A diagnosis of dermatophytosis and keratomycosis caused by T. interdigitale with loss of vision in left eye was made. The patient was treated with luliconazole cream (two applications per day) and itraconazole (100 mg, BID, PO). Complete clinical remission was achieved after 1 month. Subsequently, the patient underwent left eye enucleation in the ophthalmology department. CONCLUSIONS: In the present study, we reported a case of simultaneous dermatophytosis and keratomycosis caused by T. interdigitale, and reviewed the literature on corneal infection caused by Trichophyton. A total of 10 articles with 45 patients were published between 1973 and 2018. The pathogen of 27 patient were identified to species level. There were T. schoenleinii (17), T. mentagrophytes (4), T. verrucosum (3), T. rubrum (1), T. erinacei (1), and T. interdigitale (1). Five patients had corneal trauma, one had contact lens use history. Direct microscopic examination, fungal culture, and analysis of physiological characteristics were the main methods of identification. Early diagnosis and prompt treatment may help improve the management and outcomes.

Nicking-enhanced rolling circle amplification for sensitive fluorescent detection of cancer-related microRNAs.

In this study, a biosensing system based on nicking-enhanced rolling circle amplification (N-RCA) was proposed for the highly sensitive detection of cancer-related let-7a microRNA (miRNA). The sensing system consists of a padlock probe (PP), which contains a target recognition sequence and two binding sites for nicking endonuclease (NEase), and molecular beacon (MB) as reporting molecule. Upon hybridization with let-7a, the PP can be circularized by ligase. Then, the miRNA acted as polymerization primer to initiate rolling circle amplification (RCA). With the assistance of NEase, RCA products can be nicked on the cyclized PP and are displaced during the subsequent duplication process, generating numerous nicked fragments (NFs). These NFs not only induce another RCA reaction but also open the molecular beacons (MBs) via hybridization, leading to significantly amplified fluorescence signal. Under the optimized conditions, this method exhibits high sensitivity toward target miRNA let-7a with a detection limit of as low as 10 pM, a dynamic range of three orders of magnitude is achieved, and its family member is easily distinguished even with only one mismatched base. Meanwhile, it displays good recovery and satisfactory reproducibility in fetal bovine serum (FBS). Therefore, these merits endow the newly proposed N-RCA strategy with powerful implications for miRNA detection. Graphical abstract A biosensing system based on nicking-enhanced rolling circle amplification (N-RCA) for the highly sensitive detection of cancer-related let-7a microRNA.

Five-Year Progression of Refractive Errors and Incidence of Myopia in School-Aged Children in Western China.

BACKGROUND: To determine the change in refractive error and the incidence of myopia among school-aged children in the Yongchuan District of Chongqing City, Western China. METHODS: A population-based cross-sectional survey was initially conducted in 2006 among 3070 children aged 6 to 15 years. A longitudinal follow-up study was then conducted 5 years later between November 2011 and March 2012. Refractive error was measured under cycloplegia with autorefraction. Age, sex, and baseline refractive error were evaluated as risk factors for progression of refractive error and incidence of myopia. RESULTS: Longitudinal data were available for 1858 children (60.5%). The cumulative mean change in refractive error was -2.21 (standard deviation [SD], 1.87) diopters (D) for the entire study population, with an annual progression of refraction in a myopic direction of -0.43 D. Myopic progression of refractive error was associated with younger age, female sex, and higher myopic or hyperopic refractive error at baseline. The cumulative incidence of myopia, defined as a spherical equivalent refractive error of -0.50 D or more, among initial emmetropes and hyperopes was 54.9% (95% confidence interval [CI], 45.2%-63.5%), with an annual incidence of 10.6% (95% CI, 8.7%-13.1%). Myopia was found more likely to happen in female and older children. CONCLUSIONS: In Western China, both myopic progression and incidence of myopia were higher than those of children from most other locations in China and from the European Caucasian population. Compared with a previous study in China, there was a relative increase in annual myopia progression and annual myopia incidence, a finding which is consistent with the increasing trend on prevalence of myopia in China.

Stability of Hydrated Methylamine: Structural Characteristics and H2N···H-O Hydrogen Bonds.

Methylamine is the simplest aliphatic amine found in human urine, blood, and tissues. It is thought to play a significant part in central nervous system disturbances observed during renal and hepatic disease. In this work we have investigated the methylamine hydration clusters using a basin hopping (BH) algorithm with the density functional theory (DFT). The results presented herein yield a detailed understanding of the structure and stability for a system consisting of one methylamine molecule and up to seven waters: the most stable geometries arise from a fusion of tetramer or pentamer rings; by the geometrical parameters and topological parameters analysis, the strengths of the H2N···H-O hydrogen bonds of the global minima increase as the sizes of clusters increase, except for n = 5 where there is a slight fluctuation. This work may shed light on the form mechanism of methylamine existing in organisms and the hydration structures of larger molecules containing amino functional groups and their interaction with the water molecules nearby.

Properties and Atmospheric Implication of Methylamine-Sulfuric Acid-Water Clusters.

The presence of amines can increase aerosol formation rates. Most studies have been devoted to dimethylamine as the representative of amine; however, there have been a few works devoted to methylamine. In this study, theoretical calculations are performed on CH3NH2(H2SO4)m(H2O)n (m = 0-3, n = 0-3) clusters. In addition to the structures and energetics, we focused on determining the following characteristics: (1) the growth mechanism, (2) the hydrate distributions and the influences of humidity and temperature, (3) Rayleigh scattering properties. We explored the cluster growth mechanism from a thermodynamics aspect by calculating the Gibbs free energy of adding a water or sulfuric acid molecule step by step at three atmospherically relevant temperatures. The relative ease of the reaction at each step is discussed. From the analysis of hydrate distributions, we find that CH3NH2(H2SO4)(H2O)2, CH3NH2(H2SO4)2, and CH3NH2(H2SO4)3 are most likely to exist in the atmosphere. The general trend of hydration in all cases is more extensive with the growing relative humidity (RH), whereas the distributions do not significantly change with the temperature. Analysis of the Rayleigh scattering properties showed that both H2SO4 and H2O molecules could increase the Rayleigh scattering intensities and isotropic mean polarizabilities, with greater influence by the sulfuric acid molecules. This work sheds light on the mechanism for further research on new particle formation (NPF) containing methylamine in the atmosphere.

A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway.

Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-α5ß1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.

Successful Treatment of Refractory Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome and Paradoxical Psoriasis with Secukinumab: A Case Report.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease mainly manifested as skin and osteoarticular lesions. Herein, we describe a female patient with SAPHO syndrome exhibited paradoxical psoriasis and primary palmoplantar pustulosis (PPP) worsened during treatment with adalimumab. We then switched to secukinumab and obtained significant improvement in both skin lesions and osteoarticular pain. These findings suggest that secukinumab might be an appropriate option for patients with SAPHO syndrome who present with TNF-α-inhibitor-induced paradoxical psoriasis.

Effect of Resveratrol on MMP-2 Expression in Scleral Fibroblasts: An In Vitro Study.

PURPOSE: To investigate the effects of resveratrol (Res) on human fetal scleral fibroblasts (HFSFs) and its potential mechanism. METHODS: HFSFs were randomly divided into the Res-treated group and the control group. Following, HFSFs were treated with or without a concentration of 10 µM Res for 48 h. To detect the expression of related genes, reverse transcription quantitative PCR (RT-qPCR) and western blotting were used. The apoptosis rate of different groups was determined using flow cytometry. RESULTS: The mRNA expression of matrix metalloproteinase 2 (MMP-2), Collagen, Type I, Alpha 1 (COL1A1), Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3)" was downregulated in the Res-treatment group compared to the control group, according to RT-qPCR. Western blotting revealed that Res therapy reduced the expression of MMP-2, JAK2, P-JAK2, STAT3, P-STAT3, and Bcl-2 associated protein X (Bax) while increasing the expression of COL1A1 and B-cell lymphoma-2 (Bcl-2). Flow cytometry showed that the cell apoptosis rate was significantly lower in HFSFs treated with Res. CONCLUSIONS: In conclusion, these findings suggest that Res increases COL1A1 expression while inhibiting MMP-2 and cell apoptosis in HFSFs, possibly through modulation of the JAK2/STAT3 signaling pathway.

SNX14 inhibits autophagy via the PI3K/AKT/mTOR signaling cascade in breast cancer cells.

BACKGROUND: Sorting nexin 14 (SNX14) is a member of the sorting junction protein family. Its specific roles in cancer development remain unclear. Therefore, in this study, we aimed to determine the effects and underlying mechanisms of SNX14 on autophagy of breast cancer cells to aid in the therapeutic treatment of breast cancer. METHODS: In this study, we performed in vitro experiments to determine the effect of SNX14 on breast cancer cell growth. Moreover, we used an MCF7 breast cancer tumor-bearing mouse model to confirm the effect of SNX14 on tumor cell growth in vivo. We also performed western blotting and quantitative polymerase chain reaction to identify the mechanism by which SNX14 affects breast cancer MCF7 cells. RESULTS: We found that SNX14 regulated the onset and progression of breast cancer by promoting the proliferation and inhibiting the autophagy of MCF7 breast cancer cells. In vivo experiments further confirmed that SNX14 knockdown inhibited the tumorigenicity and inhibited the growth of tumor cells in tumor tissues of nude mice. In addition, western blotting analysis revealed that SNX14 modulate the autophagy of MCF7 breast cancer cells via the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signaling pathway. CONCLUSION: Our findings indicate that SNX14 is an essential tumor-promoting factor in the development of breast cancer.

Whole transcriptome sequencing for revealing the pathogenesis of sporotrichosis caused by Sporothrix globosa.

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.