Capsaicin combined with stem cells improved mitochondrial dysfunction in PIG3V cells, an immortalized human vitiligo melanocyte cell line, by inhibiting the HSP70/TLR4/mTOR/FAK signaling axis.

BACKGROUND: Vitiligo is a common autoimmune skin disease. Capsaicin has been found to exert a positive effect on vitiligo treatment, and mesenchymal stem cells (MSCs) are also confirmed to be an ideal cell type. This study aimed to explore the influence of capsaicin combined with stem cells on the treatment of vitiligo and to confirm the molecular mechanism of capsaicin combined with stem cells in treating vitiligo. METHODS AND RESULTS: PIG3V cell proliferation and apoptosis were detected using CCK-8 and TUNEL assays, MitoSOX Red fluorescence staining was used to measure the mitochondrial ROS level, and JC-1 staining was used to detect the mitochondrial membrane potential. The expression of related genes and proteins was detected using RT‒qPCR and Western blotting. Coimmunoprecipitation was used to analyze the protein interactions between HSP70 and TLR4 or between TLR4 and mTOR. The results showed higher expression of HSP70 in PIG3V cells than in PIG1 cells. The overexpression of HSP70 reduced the proliferation of PIG3V cells, promoted apoptosis, and aggravated mitochondrial dysfunction and autophagy abnormalities. The expression of HSP70 could be inhibited by capsaicin combined with MSCs, which increased the levels of Tyr, Tyrp1 and DCT, promoted the proliferation of PIG3V cells, inhibited apoptosis, activated autophagy, and improved mitochondrial dysfunction. In addition, capsaicin combined with MSCs regulated the expression of TLR4 through HSP70 and subsequently affected the mTOR/FAK signaling pathway CONCLUSIONS: Capsaicin combined with MSCs inhibits TLR4 through HSP70, and the mTOR/FAK signaling pathway is inhibited to alleviate mitochondrial dysfunction and autophagy abnormalities in PIG3V cells.

Combination of 308-nm excimer laser and piperine promotes melanocyte proliferation, migration, and melanin content production via the miR-328/SFRP1 axis.

OBJECTIVE: Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. METHODS: Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. RESULTS: The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/ß-catenin signaling pathway. CONCLUSION: The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/ß-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.

A Large-Scale Exome-Wide Association Study Identifies Novel Germline Mutations in Lung Cancer.

Rationale: Genome-wide association studies have identified common variants of lung cancer. However, the contribution of rare exome-wide variants, especially protein-coding variants, to cancers remains largely unexplored. Objectives: To evaluate the role of human exomes in genetic predisposition to lung cancer. Methods: We performed exome-wide association studies to detect the association of exomes with lung cancer in 30,312 patients and 652,902 control subjects. A scalable and accurate implementation of a generalized mixed model was used to detect the association signals for loss-of-function, missense, and synonymous variants and gene-level sets. Furthermore, we performed association and Bayesian colocalization analyses to evaluate their relationships with intermediate exposures. Measurements and Main Results: We systematically analyzed 216,739 single-nucleotide variants in the human exome. The loss-of-function variants exhibited the most notable effects on lung cancer risk. We identified four novel variants, including two missense variants (rs202197044TET3 [Pmeta (P values of meta-analysis) = 3.60 × 10-8] and rs202187871POT1 [Pmeta = 2.21 × 10-8]) and two synonymous variants (rs7447927TMEM173 [Pmeta = 1.32 × 10-9] and rs140624366ATRN [Pmeta = 2.97 × 10-9]). rs202197044TET3 was significantly associated with emphysema (odds ratio, 3.55; Pfdr = 0.015), whereas rs7447927POT1 was strongly associated with telomere length (ß = 1.08; Pfdr (FDR corrected P value) = 3.76 × 10-53). Functional evidence of expression of quantitative trait loci, splicing quantitative trait loci, and isoform expression was found for the four novel genes. Gene-level association tests identified several novel genes, including POT1 (protection of telomeres 1), RTEL1, BSG, and ZNF232. Conclusions: Our findings provide insights into the genetic architecture of human exomes and their role in lung cancer predisposition.

Cascade Cyclization of 1,5-Diynols and (RO)2P(O)SH to Construct Benzo[b]fluorenyl S-Alkyl Phosphorothioates under Catalyst-Free Conditions.

An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.

Photoexcited Cryptochrome2 Interacts Directly with TOE1 and TOE2 in Flowering Regulation.

Cryptochromes are photolyase-like, blue-light (BL) photoreceptors found in various organisms. Arabidopsis (Arabidopsis thaliana) cryptochromes (CRYs; CRY1, and CRY2) mediate many light responses including photoperiodic floral initiation. Cryptochromes interact with COP1 and SPA1, causing the stabilization of CONSTANS (CO) and promotion of FLOWERING LOCUS T (FT) transcription and flowering. The AP2-like transcriptional factor TOE1 negatively regulates FT expression and flowering by indirectly inhibiting CO transcriptional activation activity and directly binding to FT Here, we demonstrate that CRY1 and CRY2 physically interact with TOE1 and TOE2 in a BL-dependent manner in flowering regulation. Genetic studies showed that mutation of TOE1 and TOE2 partially suppresses the late-flowering phenotype of cry1 cry2 mutant plants. BL-triggered interactions of CRY2 with TOE1 and TOE2 promote the dissociation of TOE1 and TOE2 from CO, resulting in alleviation of their inhibition of CO transcriptional activity and enhanced transcription of FT Furthermore, we show that CRY2 represses TOE1 binding to the regulatory element within the Block E enhancer of FT These results reveal that TOE1 and TOE2 act as downstream components of CRY2, thus partially mediating CRY2 regulation of photoperiodic flowering through modulation of CO activity and FT transcription.

Antifungal Activity and Action Mechanism Study of Coumarins from Cnidium monnieri Fruit and Structurally Related Compounds.

The increasing resistance of plant diseases caused by phytopathogenic fungi highlights the need for highly effective and environmentally benign agents. The antifungal activities of Cnidium monnieri fruit extracts and five isolated compounds as well as structurally related coumarins against five plant pathogenic fungi were evaluated. The acetone extract, which contained the highest amount of five coumarins, showed strongest antifungal activity. Among the coumarin compounds, we found that 4-methoxycoumarin exhibited stronger and broader antifungal activity against five phytopathogenic fungi, and was more potent than osthol. Especially, it could significantly inhibit the growth of Rhizoctonia solani mycelium with an EC50 value of 21 µg mL-1 . Further studies showed that 4-methoxycoumarin affected the structure and function of peroxisomes, inhibited the ß-oxidation of fatty acids, decreased the production of ATP and acetyl coenzyme A, and then accumulated ROS by damaging MMP and the mitochondrial function to cause the cell death of R. solani mycelia. 4-Methoxycoumarin presented antifungal efficacy in a concentration- dependent manner in vivo and could be used to prevent the potato black scurf. This study laid the foundation for the future development of 4-methoxycournamin as an alternative and friendly biofungicide.

The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.

Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus, against Botrytis cinerea; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea. The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea, with an EC50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea. This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi.

Association between diet quality and obesity indicators among the working-age adults in Inner Mongolia, Northern China: a cross-sectional study.

BACKGROUND: Obesity is a major risk factor for the global burden of disease in countries that are economically developed or not. This study aimed to investigate the association between diet quality and obesity indicators applying DASH and aMed. METHODS: This cross-sectional study on adult nutrition and chronic disease in Inner Mongolia (n = 1320). Dietary data were collected using 24-h diet recall for 3 consecutive days and weighing method. DASH and aMed were used to assess the dietary quality. WC, BMI and WC-BMI were used as obesity indicators. Logistic regression models were used to examine the associations between diet quality and obesity indicators. RESULTS: Higher diet quality, assessed by DASH, was only associated with WC. The odds ratio (OR) for abdominal obesity in the highest tertile of DASH scores compared with the lowest was 0.71 (95% confidence interval (CI) 0.53, 0.96; Ptrend = 0.03). Furthermore, aMed was inversely associated with obesity indicators. OR for abdominal obesity in the highest tertile of aMed score compared with the lowest were 0.63 (95% CI 0.47, 0.87; Ptrend = 0.005) and 0.57 (95% CI 0.41, 0.77; Ptrend = 0.02) for overweight and obesity, respectively, and 0.60 (95% CI 0.44, 0.81; Ptrend = 0.02) for high obesity risk. CONCLUSIONS: Our findings suggest that dietary quality assessed using aMed is more closely associated with obesity than assessment using DASH in working-age adults in Inner Mongolia. The Mediterranean diet can be recommended as a healthy diet to control weight.

Bioassay-guided isolation of two antifungal compounds from Magnolia officinalis, and the mechanism of action of honokiol.

Magnolia officinalis, as a well-known herb worldwide, has been widely used to treat multiple diseases for a long time. In this study, the petroleum ether extract from M. officinalis showed effective antifungal activity against seven plant pathogens (particularly against R. solani with an inhibition rate of 100.00% at 250 µg/mL). Honokiol and magnolol, isolated by the bioassay-guided method, exhibited greater antifungal activity than tebuconazole (EC50 = 3.07 µg/mL, p ≤ 0.001) against R. solani, which EC50 values were 2.18 µg/mL and 3.48 µg/mL, respectively. We used transcriptomics to explore the mechanism of action of honokiol against R. solani. Results indicated that honokiol may exert antifungal effects by blocking the oxidative phosphorylation metabolic pathway. Further studies indicated that honokiol induced ROS overproduction, disrupted the mitochondrial function, affected respiration, and blocked the TCA cycle, which eventually inhibited ATP production. Besides, honokiol also damaged cell membranes and caused morphological changes. This study demonstrated that the lignans isolated from M. officinalis possess the potential to be developed as botanical fungicides.

[Network pharmacology study on potential active components in volatile oil of Dictamni Cortex].

There are many chemical components in the volatile oil of Dictamni Cortex. The complex network relationship of "component-target-disease" can be revealed by using the network pharmacology method, and the mechanism of the efficacy of Dictamni Cortex can be revealed. In this study, we used Swiss Target Prediction database to predict the target of action, STRING database to build protein interaction network, and Cytoscape software to build "component-target-disease" network. The results showed that the antibacterial, anti-inflammatory and antiallergic effects of Dictamni Cortex were closely related to the components of thymol methyl ether, elemenol, anethole, and the related targets of each component were cross-linked to play a multi-target pharmacodynamic role. This study laid a foundation for the study of the effective substance basis and quality control evaluation of the Dictamni Cortex, and provided a scientific basis for further revealing its mechanism.

[UFLC-Q-TOF-MS fingerprints of rhizome of Curcuma phaeocaulis and its vinegar processed products and inhibitory effect on thrombosis].

Both raw and vinegar products of the rhizome of Curcuma phaeocaulis are common drugs for promoting blood circulation and removing blood stasis in traditional Chinese medicine,which could be reflected in the inhibition of tail thrombosis in mice. As the traditional processing theory instructs,vinegar tastes sour and bitter,but can activate blood circulation and remove stasis after being infiltrated into the rhizome of C. phaeocaulis as an excipient. In this study,under the help of the ultrafast liquid chromatography-quadrupole time-offlight mass spectrometry( UFLC-Q-TOF-MS),the spectrum-effect relationship between the inhibition of tail thrombosis in mice and the rhizome of C. phaeocaulis both before and after the vinegar processing,were established to explore the functional changes of blood circulation and stasis after vinegar process. Based on the peak area from the fingerprint of UFLC-Q-TOF-MS of the alcohol extracts from the raw and vinegar-processed rhizome of C. phaeocaulis and their efficacy for inhibiting tail thrombosis,the correlation between the chromatography of UFLC-Q-TOF-MS and the inhibition of tail thrombosis in mice were analyzed by orthogonal partial least squares discriminant analysis( OPLS-DA) method. The results,produced by Simca-P software,showed that effective components consisted of eight peaks 16,24( aromadendrene oxide),3,11,22( dehydro-α-curcumene),19[( R)-(-)-α-curcumene],23 and 10 from the fingerprint,making great contribution to distinguish C. phaeocaulis raw products and the corresponding vinegar processed products. Therefore,from the perspective of inhibiting the formation of tail thrombosis in mice,the marker components could be found through the spectrum-effect relationship to distinguish C.phaeocaulis raw and vinegar products. This study provided new basis to explain the difference between the raw and the processed products of traditional Chinese medicine in the functional change of promoting blood circulation and removing blood stasis.

Effect of starter culture on microbiological, physiochemical and nutrition quality of Xiangxi sausage.

Fermented sausages have a long tradition originating from China. In this study, three starter microorganisms including Pediococcus pentosaceus (P), Staphylococcus xylosus (S), and a combination of P. pentosaceus and S. xylosus (P + S) were conducted for the manufacture of traditional Xiangxi (a city in China) fermented sausages. The physicochemical changes of the above three kinds of sausages during fermentation were studied and discussed, and also compared with these properties on the natural fermented sausage (N, i.e., control). The results revealed that five kinds of bacterial phases were existed at different fermentation stages in N, P, S and P + S fermented sausages, respectively. The microbiological data showed that an initial enterobacteria count of approximately 5.3 log CFU/g for all four batches of sausages. The enterobacteria count in the inoculated sausages of P and P + S groups decreased significantly to about 1 log CFU/g whereas group N and S had a count of about 3.3 log CFU/g after fermentation. In the early stages of fermentation, the pH rapidly decreased below 5.3. FAA and FFA were significantly increased in all groups and TBARS value in group P was higher than that of the other three groups. In conclusion, starter cultures can be used to improve the hygiene level of Xiangxi sausages without significant effects on pH, AW, and nitrite residue.

Attentional bias towards sleep-related stimuli in insomnia disorder: a behavioural and ERP study.

Many studies have used behavioural experiments to show an attentional bias towards sleep-related stimuli in people with insomnia disorder. A measurement of event-related potential is needed to investigate the cognitive processing mechanism of the attentional process. The present study used the emotional Stroop paradigm and event-related potentials to measure attentional bias towards sleep-negative, sleep-positive and sleep-unrelated neutral words. The study comprised 16 participants with insomnia disorder and 15 participants who were good sleepers. Behavioural data indicated that there was a significant interference effect of sleep-positive words between the insomnia group and the good sleepers, and a marginally significant interference effect from sleep-negative words between groups. In the insomnia group, event-related potential data showed that sleep-negative words elicited higher amplitudes of P1 and N1 components than did sleep-positive and sleep-unrelated words. Our results provide evidence for the early cognitive processing of sleep-negative stimuli, which suggests that the psychological treatment of insomnia could benefit from addressing early hypervigilance towards these stimuli.

Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas.

Glyceraldehyde-3-phosphate dehydrogenase, is one of the most investigated housekeeping genes and widely used as an internal control in analysis of gene expression levels. The present study was designed to assess whether GAPDH is associated with cancer cell growth and progression and, therefore may not be a good internal control in cancer research. Our results from clinical tissue studies showed that the levels of GAPDH protein were significantly up-regulated in lung squamous cell carcinoma tissues, compared with the adjacent normal lung tissues, and this was confirmed by western blotting and immunohistochemistry. GAPDH knockdown by siRNA resulted in significant reductions in proliferation, migration, and invasion of lung squamous carcinoma cells in vitro. In a nude mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell proliferation and migration/invasion in vivo. In summary, GAPDH may not be an appropriate internal control for gene expression studies, especially in cancer research. The role of GAPDH in cancer development and progression should be further examined in pre-clinical and clinical studies.

A cross-trait study of lung cancer and its related respiratory diseases based on large-scale exome sequencing population.

Background: Genome-wide association studies (GWASs) explain the genetic susceptibility between diseases and common variants. Nevertheless, with the appearance of large-scale sequencing profiles, we could explore the rare coding variants in disease pathogenesis. Methods: We estimated the genetic correlation of nine respiratory diseases and lung cancer in the UK Biobank (UKB) by linkage disequilibrium score regression (LDSC). Then, we performed exome-wide association studies at single-variant level and gene-level for lung cancer and lung cancer-related respiratory diseases using the whole-exome sequencing (WES) data of 427,934 European participants. Cross-trait meta-analysis was conducted by association analysis based on subsets (ASSET) to identify the pleiotropic variants, while in-silico functional analysis was performed to explore their function. Causal mediation analysis was used to explore whether these pleiotropic variants lead to lung cancer is mediated by affecting the chronic respiratory diseases. Results: Five respiratory diseases [emphysema, pneumonia, asthma, chronic obstructive pulmonary disease (COPD), and fibrosis] were genetically correlated with lung cancer. We identified 102 significant independent variants at single-variant levels for lung cancer and five lung cancer-related diseases. 15:78590583:G>A (missense variant in CHRNA5) was shared in lung cancer, emphysema, and COPD. Meanwhile, 14 significant genes and 87 suggestive genes were identified in gene-based association tests, including HSD3B7 (lung cancer), SRSF2 (pneumonia), TNXB (asthma), TERT (fibrosis), MOSPD3 (emphysema). Based on the cross-trait meta-analysis, we detected 145 independent pleiotropic variants. We further identified abundant pathways with significant enrichment effects, demonstrating that these pleiotropic genes were functional. Meanwhile, the proportion of mediation effects of these variants ranged from 6 to 23 (emphysema: 23%; COPD: 20%; pneumonia: 20%; fibrosis: 7%; asthma: 6%) through these five respiratory diseases to the incidence of lung cancer. Conclusions: The identified shared genetic variants, genes, biological pathways, and potential intermediate causal pathways provide a basis for further exploration of the relationship between lung cancer and respiratory diseases.

Proteome-wide Mendelian randomization identifies causal plasma proteins in lung cancer.

Plasma proteins are promising biomarkers and potential drug targets in lung cancer. To evaluate the causal association between plasma proteins and lung cancer, we performed proteome-wide Mendelian randomization meta-analysis (PW-MR-meta) based on lung cancer genome-wide association studies (GWASs), protein quantitative trait loci (pQTLs) of 4,719 plasma proteins in deCODE and 4,775 in Fenland. Further, causal-protein risk score (CPRS) was developed based on causal proteins and validated in the UK Biobank. 270 plasma proteins were identified using PW-MR meta-analysis, including 39 robust causal proteins (both FDR-q < 0.05) and 78 moderate causal proteins (FDR-q < 0.05 in one and p < 0.05 in another). The CPRS had satisfactory performance in risk stratification for lung cancer (top 10% CPRS:Hazard ratio (HR) (95%CI):4.33(2.65-7.06)). The CPRS [AUC (95%CI): 65.93 (62.91-68.78)] outperformed the traditional polygenic risk score (PRS) [AUC (95%CI): 55.71(52.67-58.59)]. Our findings offer further insight into the genetic architecture of plasma proteins for lung cancer susceptibility.

Direct Synthesis of Benzo[b]fluorenyl Thiophosphates via Tandem Cyclization of Diynols with (RO)2P(O)SH.

A general and metal-free protocol for the construction of benzo[b]fluorenyl thiophosphates was developed through the cascade cyclization of easily prepared diynols and (RO)2P(O)SH, with water as the only byproduct. The novel transformation involved the allenyl thiophosphate as the key intermediate, followed by Schmittel-type cyclization to achieve the desired products. Notably, (RO)2P(O)SH acted not only as a nucleophile but also as an acid-promoter to initiate the reaction.

Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells.

The efficacy of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, has been evaluated in glioblastoma (GBM) through preclinical and clinical trials. However, the underlying mechanism of osimertinib-induced GBM cell death and the underlying resistance mechanism to osimertinib remains unclear. Here, we demonstrate that Osimertinib induces paraptosis in GBM cells, as evidenced by the formation of cytoplasmic vacuoles, accumulation of ubiquitinated proteins, and upregulation of endoplasmic reticulum (ER) stress markers like CHOP. Additionally, neither apoptosis nor autophagy was involved in the osimertinib-induced cell death. RNAseq analysis revealed ER stress was the most significantly downregulated pathway upon exposure to osimertinib. Consistently, pharmacologically targeting the PERK-eIF2α axis impaired osimertinib-induced paraptosis. Notably, we show that the expression of thyroid receptor-interacting protein 13 (TRIP13), an AAA+ATPase, alleviated osimertinib-triggered paraptosis, thus conferring resistance. Intriguingly, MK-2206, an AKT inhibitor, downregulated TRIP13 levels and synergized with Osimertinib to suppress TRIP13-induced high GBM cell growth in vitro and in vivo. Together, our findings reveal a novel mechanism of action associated with the anti-GBM effects of osimertinib involving ER stress-regulated paraptosis. Furthermore, we identify a TRIP13-driven resistance mechanism against Osimertinib in GBM and offer a combination strategy using MK-2206 to overcome such resistance.

Exploring boron applications in modern agriculture: Antifungal activities and mechanisms of phenylboronic acid derivatives.

BACKGROUND: The unreasonable use of chemical fungicides causes common adverse consequences that not only affect the environment, but also cause resistance and resurgence problems of plant pathogens, which are extremely harmful to human health, the economy, and the environment. Based on the rich biological activities of boron-based compounds, 82 phenylboronic acid derivatives were selected and their antifungal activities against six agricultural plant pathogens were determined. Combined with transcriptomics tools, the mechanism of action of compound A49 (2-chloro-5-trifluoromethoxybenzeneboronic acid) against Botrytis cinerea Pers (B. cinerea) was studied. RESULTS: The EC50 values of compounds A24, A25, A30, A31, A36, A41, A49 and B23 against all six fungi were under 10 µg/mL. Compound A49 displayed significant activity against B. cinerea (EC50 = 0.39 µg/mL), which was better than that of commercial fungicide boscalid (EC50 = 0.55 µg/mL). A49 not only inhibited the germination of B. cinerea spores, but also caused abnormal cell morphology, loss of cell membrane integrity, enhanced cell membrane permeability, and accumulation of intracellular reactive oxygen species. Further findings showed that A49 reduced cellular antioxidant activity, and peroxidase and catalase activities. Transcriptomic results indicated that A49 could degrade intracellular redox processes and alter the metabolism of some amino acids. Meanwhile, A49 showed obvious activity in vivo and low cytotoxicity to mammal cells. CONCLUSION: The boron-containing small molecule compounds had high efficiency and broad-spectrum antifungal activities against six plant pathogens, and are expected to be candidate compounds for a new class of antifungal drugs. © 2023 Society of Chemical Industry.

Higher expression of Caveolin-1 inhibits human small cell lung cancer (SCLC) apoptosis in vitro.

Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, and its treatment is closely associated with apoptosis. Caveolin-1 plays an important role in the development of a variety of human cancers. This study sought to investigate the influence of Caveolin-1 on the apoptosis of SCLC in vitro. We demonstrate that higher expression of Caveolin-1 leads to inhibition of cisplatin and Ultraviolet Radiation (UVR)-induced apoptosis in SCLC cells; and also could decrease caspase-3 activity and increase the stability of Bcl-2 at the protein level. Our findings illuminate a potential molecular mechanism regarding CAV-1's role as anti-apoptosis protein.