Efficacy and adverse reactions of fractional CO2 lasers for treating papular acne scars: a retrospective study of 35 patients.

Papular acne scars are a special type of acne scar, and the prevalence and treatment of this disease have rarely been reported in the literature; moreover, the prevalence of this disease is often neglected, and treatment is difficult. Our study revealed a high prevalence of this type of acne scar in the clinic and explored an effective and safe method. This retrospective study aimed to analyse the prevalence of papular acne scarring among patients attending our Dermatology Laser Clinic and evaluate the clinical efficacy of fractional CO2 lasers. We retrieved the data of 370 patients with acne scarring who visited our hospital between April 2021 and November 2022 and analysed the prevalence of papillary acne scarring among them. Among these patients, 35 underwent CO2 laser treatment using an artificial grid pattern. A total of three treatments were administered, with a two-month interval between each session. Scar assessment was conducted using the Global Scar Scale (GSS) and the Acne Scar Clinical Assessment (ECCA) scale, along with physician visual evaluation and patient satisfaction surveys, both before the first treatment and one month after the final treatment. Adverse reactions were recorded during follow-up visits after each treatment. Among the 370 patients with acne scarring, 128 exhibited papular acne scarring, resulting in a prevalence rate of 34.6%. Among them, 37.5% were male and 32.6% were female. A total of 90.6% of patients had combined other types of acne scarring, while 9.4% had papular acne scarring exclusively. Following CO2 laser grid treatment, there was a significant reduction in GSS scores and ECCA values, accompanied by a noticeable improvement in physician visual evaluation and patient satisfaction scores. Papular acne scarring has a relatively high incidence rate, and there is no significant sex difference. It often coexists with other types of acne scarring. CO2 laser treatment using an artificial grid pattern effectively improved papular acne scarring with a good safety profile.

Effects of combined ultrasound and calcium ion pretreatments on polyphenols during mung bean germination: Exploring underlying mechanisms.

Mung beans were pretreated with a combination of ultrasonic and calcium ion to enhance the polyphenol content and antioxidant capacity during germination. Changes in polyphenol content and antioxidant capacity during germination, along with underlying mechanisms, were investigated. Both single ultrasound and combined ultrasound-Ca2+ pretreatments significantly increased the polyphenol content and enhanced the antioxidant capacity (p < 0.05) of mung beans depending on germination period. Among 74 polyphenolic metabolites identified in germinated mung beans, 50 were differential. Notably, 23 of these metabolites showed a significant positive correlation with antioxidant activity. Ultrasound pretreatment promoted flavonoid biosynthesis, whereas ultrasound-Ca2+ pretreatment favored the tyrosine synthesis pathway. Polyphenol composition and accumulation changes were mainly influenced by metabolic pathways like flavonoid, isoflavonoid, anthocyanin, and flavone/flavonol biosynthesis. The results suggest that ultrasound alone or combined with calcium ion pretreatments effectively enhance mung bean polyphenol content and antioxidant capacity during germination.

Distribution and effects of microplastics as carriers of heavy metals in river surface sediments.

There are few studies on microplastics (MPs) in urban river sediments compared to oceans, soils, and even rivers. In this study, the seasonal abundance of MPs, as well as their influencing factors on heavy metal adsorption in river sediments of the Ancient Canal of Zhenjiang City, China, were investigated for the first time. Through on-site sampling, microscopic observation, Raman spectroscopy, scanning electron microscopy, and high-temperature digestion, the abundance, shape, color, particle size, type, and surface characteristics of MPs in Ancient Canal sediments in different seasons, as well as the influencing factors of MPs as heavy metal carriers in different seasons, were analyzed. The results showed that the average abundance of MPs is 2049.09 ± 883.78 and 2216.36 ± 826.21 items kg-1 dry sediments in summer and winter, respectively, and different sites change significantly. In addition, particle sizes, types, colors, and shapes of MPs exhibited seasonal variations. Four MPs shapes were mainly observed: fibers, fragments, particles, and films. Among them, MPs in summer sediments are mainly fiber, and MPs in winter sediments are mainly particles. In the sediment in summer and winter, transparent MPs and small-size (<0.5 mm) MPs are the main ones, where the abundance of MPs decreased with increasing MPs size. The main MPs species are polyvinyl chloride (PVC), polystyrene (PS), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate (PC), and polyethylene (PE), with PP being the predominant MPs in the sediments in different seasons. Scanning electron microscopy-energy dispersive spectrometer (SEM-EDS) revealed that the surfaces of the MPs were characterized by rough, porous, cracked, and torn, with the attachment of various heavy metal elements, and all of the heavy metal elements accumulated to different degrees on the MPs. There was a significant positive correlation (p < 0.05) between the Mn content in the MPs and the Mn content in the sediments in winter, suggesting that the Mn in the MPs in winter may be derived from the sediments. In addition, the type, shape, size, and color of MPs affect the adsorption capacity of heavy metals. Most of the adsorption of MPs on Pb showed a significant negative correlation, and the adsorption of MPs on Cr, Zn, Cu, Cd, and Mn showed a significant positive correlation. MPs can be used as carriers of heavy metals, which will further enhance the hazards of living organisms and pose a potential threat to the safety of the urban river environment.

Food Protein Nanofibril Gels: From Conditions, Types and Properties to Applications.

Many food proteins can be assembled into nanofibrils under pH conditions far from the isoelectric point and with a low ionic strength by heating them for a long period. These food protein nanofibrils (FPN) have outstanding functional and biological properties and are considered sustainable biomaterials in many fields. In this study, we review the recent developments in FPN gels and introduce the key factors in promoting food protein self-assembly in order to create functional gels. The major variables discussed are the morphology of nanofibrils, protein concentration, heating time, and the type and concentration of salts. We also highlight current advances in the formation and properties of different types of FPN gels. In addition, the various applications of FPN gels in bioactive and nutrient delivery, adsorbents for CO2 and toxic pollutants, cell scaffolding biomaterials, biosensors, and others are introduced and discussed.

Extractions, Contents, Antioxidant Activities and Compositions of Free and Bound Phenols from Kidney Bean Seeds Represented by 'Yikeshu' Cultivar in Cold Region.

To thoroughly understand the profile of phenolic phytochemicals in kidney bean seeds cultivated in a cold region, the extractions, contents, antioxidant activities, compositions of free and bound phenols in the seed coat and cotyledon, and also relevant color attributes, were investigated. The results indicated that ultrasound-assisted extraction was an efficient method for free phenols. The bound phenols in seed coat and cotyledon were released more efficiently by alkali-acid and acid-alkali sequential hydrolysis, respectively. Under the optimized extractions, total phenols (TPC), flavonoids (TFC), and anthocyanins (TAC) ranged in 7.81-32.89 mg GAE/g dw, 3.23-15.65 mg RE/g dw, and 0-0.21 mg CE/g dw in the whole seeds of the five common kidney beans. There was a big difference in phenolic distribution between red and white seeds. From whole seed, the phenols in the four red cultivars mainly existed in free state (78.84%) and seed coat (71.56%), while the phenols in the white 'Sark' divided equally between free (51.18%) and bound (48.82%) states and consisted chiefly in cotyledon (81.58%). The correlation analyses showed that the antioxidant activities were significantly and positively correlated with TPC and TFC. The phenolic attributes were closely associated with the color of the seed coat. Red seeds had higher total contents of phenols than white seeds. TAC had a positively significant correlation with redness. Brightness and yellowness showed a negatively significant correlation with TPC, TFC, and antioxidant capacities, which were necessarily linked with redness degree and spot in red seeds. The spotted red 'Yikeshu' with the most outstanding performance on phenolic attributes was selected to analyze phenolic compounds with UHPLC-QE-MS. Among the 85 identified phenolics, 2 phenolic acids and 10 flavonoids were dominant. The characteristic phenolics in free and bound states were screened in both seed coat and cotyledon, respectively. The available information on the phenolic profile may expand the utilization of kidney beans as a nutritional ingredient in the food industry.

Inhibition of Glycyrrhiza Polysaccharide on Human Cytochrome P450 46A1 in vitro and in vivo: Implications in Treating Neurological Diseases.

BACKGROUND: Cytochrome P450 (CYP) 46A1, also known as cholesterol 24S-hydroxylase, is essential for maintaining the homeostasis of cholesterol in the brain and serves as a therapeutic target of neurodegenerative disorders and excitatory neurotoxicity. N-methyl-d-aspartate receptor (NMDAR) is a prototypical receptor for the excitatory neurotransmitter glutamate and can be specifically regulated by 24S-hydroxycholesterol (24S-HC). Glycyrrhiza is one of the most widely used herbs with broad clinical applications, which has several pharmacological activities, such as clearing heat and detoxifying, moistening the lung and relieving cough, analgesic, neuroprotective outcomes, and regulating a variety of drug activities. Glycyrrhiza is a commonly used herb for the treatment of epileptic encephalopathy. However, whether glycyrrhiza can interfere with the activity of CYP46A1 remains unknown. OBJECTIVE: This study aimed to investigate the regulating effects of glycyrrhiza polysaccharides (GP) on CYP46A1-mediated cholesterol conversion, as well as in the modulation of related proteins. MATERIALS AND METHODS: The effects of glycyrrhiza polysaccharide (GP) on the activity of CYP46A1 were investigated in vivo and in vitro. Moreover, the potential regulatory effects of GP on the expressions of CYP46A1, HMG-CoA reductase (HMGCR), and NMDAR were also detected. RESULTS: The in vitro results demonstrated that glycyrrhiza polysaccharide (GP), as the main water-soluble active component of glycyrrhiza, remarkably inhibited the activity of CYP46A1 in a non-competitive mode with a Ki value of 0.7003 mg/ml. Furthermore, the in vivo experiments verified that GP markedly decreased the contents of 24S-HC in rat plasma and brain tissues as compared to the control. More importantly, the protein expressions of CYP46A1, GluN2A, GluN2B, and HMG-CoA reductase (HMGCR) in rat brains were all downregulated, whereas the mRNA expressions of CYP46A1 and HMGCR were not significantly changed after treatment with GP. CONCLUSION: GP exhibits a significant inhibitory effect on CYP46A1 activity in vitro and in vivo, and the protein expressions of CYP46A1, HMGCR, and NMDAR are also inhibited by GP, which are of considerable clinical significance for GP's potential therapeutic role in treating neurological diseases.

Phenotypic and genomic insights into mutant with high nattokinase-producing activity induced by carbon ion beam irradiation of Bacillus subtilis.

Nattokinase (NK) is found in fermented foods and has high fibrinolytic activity, which makes it promising for biological applications. In this study, a mutant strain (Bacillus subtilis ZT-S1, 5529.56 ± 183.59 U/mL) with high NK-producing activity was obtained using 12C6+ heavy ion beam mutagenesis for the first time. The surface morphology of B. subtilis is also altered by changes in functional groups caused by heavy ion beams. Furthermore, B. subtilis ZT-S1 required more carbon and nitrogen sources and reached stabilization phase later. Comparative genome analysis revealed that most of the mutant implicated genes (oppA, appA, kinA, spoIIP) were related to spore formation. And the affected rpoA is related to the synthesis of the NK-coding gene aprE. In addition, the B. subtilis ZT-S1 obtained by mutagenesis had good genetic stability. This study further explores the factors affecting NK activity and provides a promising microbial resource for NK production in commercial applications.

Bruceine A alleviates alcoholic liver disease by inhibiting AIM2 inflammasome activation via activating FXR.

BACKGROUND: Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PURPOSE: We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). METHODS: Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. RESULTS: BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. CONCLUSION: BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.

Alpha-lipoic Acid Prevents Bone Loss in Type 2 Diabetes and Postmenopausal Osteoporosis Coexisting Conditions by Modulating the YAP/Glut4 Pathway.

This study aims to characterize the bone-protecting effects of Alpha-lipoic acid (ALA), a potent antioxidant, against the detrimental effects of the coexistence of type 2 diabetes mellitus (T2DM) and postmenopausal osteoporosis (POP) and identify the possible mechanisms with particular reference to its modulation of YAP/Glut4 pathway. The T2DM and POP coexisting model was induced in mice by high fat diet (HFD) + Streptozocin (STZ) + ovariectomy (OVX). The mice in the treatment groups were given ALA for 10 weeks. In the in vitro study, MC3T3-E1 cells were induced with 500 µM methylglyoxal for 24 h with or without pretreatment with ALA for 24 h. The oxidative and antioxidative biomarkers, bone microarchitecture, histo-morphology, and related protein expression of apoptosis, osteogenic differentiation and the YAP/Glut4 pathway were detected. The results showed ALA could improve glucose tolerance, inhibit oxidative stress and apoptosis and alleviate bone loss. Further study by siRNA technology revealed that the YAP/Glut4 pathway was implicated in the pathogenesis of bone loss due to the coexistence of T2DM and POP. Taken together, the present study has demonstrated for the first time that ALA exerts potent protective effects against bone loss in T2DM and POP coexisting conditions by modulating the YAP/Glut4 pathway.

Effect of modified okara insoluble dietary fibre on the quality of yoghurt.

The aim of this study was to investigate the potential of adding soya bean dregs insoluble dietary fibre (IDF) modified by jet cavitation combined with cellulase to yoghurt to improve its functional properties (Yoghurt was prepared by adding 10 µL of yoghurt fermenter to 100 mL of milk, fermented to pH 4.5 in a constant temperature incubator at 42 °C, and then stored in a refrigerator at 4 °C after adding IDF separately). The results showed that the modified IDF had a rough structure with high water-holding capacity and sodium cholate adsorption capacity. The addition of modified IDF improved the pH, hardness, and elasticity of the yoghurt. During the entire storage period, the titratable acidity and whey precipitation rate of the modified IDF yoghurt gradually increased, and antioxidant activity gradually decreased, and its titratable acidity, whey precipitation rate, and antioxidant activity had a significant advantage compared with those of the blank group yoghurt. In conclusion, the modified soya bean dregs IDF-added yoghurt prepared by jet cavitation combined with the cellulase method has the potential for sodium cholate adsorption capacity and antioxidant activity, which can confer unique functional properties and improve the pH, texture, and reduce whey precipitation of yoghurt. This study provides a scientific basis for the application of soya bean dregs IDF as a fibre fortifier in yoghurt production and suggests innovative ideas for the design of functional dairy products.

FXR overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in alcoholic liver disease.

BACKGROUND AND PURPOSE: Alcoholic liver disease (ALD), a metabolic liver disease caused by excessive alcohol consumption, has attracted increasing attention due to its high prevalence and mortality. Up to date, there is no effective and feasible treatment method for ALD. This study was to investigate whether Farnesoid X receptor (FXR, NR1H4) can alleviate ALD and whether this effect is mediated by inhibiting absent in melanoma 2 (AIM2) inflammasome activation. METHODS: The difference in FXR expression between normal subjects and ALD patients was analyzed using the Gene Expression Omnibus (GEO) database. Lieber-DeCarli liquid diet with 5% ethanol (v/v) (EtOH) was adopted to establish the mouse ALD model. Liver histopathological changes and the accumulation of lipid droplets were assessed by H&E and Oil Red O staining. Quantitative real-time PCR, Western blotting analysis and immunofluorescence staining were utilized to evaluate the expression levels of related genes and proteins. DCFH-DA staining was adopted to visualize reactive oxidative species (ROS). RESULTS: FXR was distinctly downregulated in liver tissues of patients with steatosis compared to normal livers using the GEO database, and in ethanol-induced AML-12 cellular steatosis model. FXR overexpression ameliorated hepatic lipid metabolism disorder and steatosis induced by ethanol by inhibiting the expression of genes involved in lipid synthesis and inducing the expression of genes responsible for lipid metabolism. Besides, FXR overexpression inhibited ethanol-induced AIM2 inflammasome activation and alleviated oxidative stress and ROS production during ethanol-induced hepatic steatosis. However, when FXR was knocked down, the results were completely opposite. CONCLUSIONS: FXR attenuated lipid metabolism disorders and lipid degeneration in alcohol-caused liver injury and alleviated oxidative stress and inflammation by inhibiting AIM2 inflammasome activation.

Coenzyme Q10 Protects Against Hyperlipidemia-Induced Osteoporosis by Improving Mitochondrial Function via Modulating miR-130b-3p/PGC-1α Pathway.

In hyperlipidemia-induced osteoporosis, bone marrow mesenchymal stem cells (BMSCs) differentiate into more adipocytes than osteoblasts, leading to decreased bone formation. It is vital to elucidate the effects of hyperlipidemia on bone metabolism and seek new agents that regulate adipocyte-osteoblast lineage allocation. CoQ10, a rate-limiting coenzyme of the mitochondrial respiratory chain, has been reported to decrease oxidative stress and lipid peroxidation by functioning as a mitochondrial antioxidant. However, its effect on hyperlipidemia-induced osteoporosis remains unknown. Here, we analyzed the therapeutic mechanisms of CoQ10 on hyperlipidemia-induced osteoporosis by using high-fat diet (HFD)-treated ApoE-/- mice or oxidized low-density lipoprotein (ox-LDL)-treated BMSCs. The serum lipid levels were elevated and bone formation-related markers were decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, which could be reversed by CoQ10. Additionally, PGC-1α protein expression was decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, accompanied by mitochondrial dysfunction, decreased ATP content and overgeneration of reactive oxygen species (ROS), which could also be antagonized by CoQ10. Furthermore, PGC-1α knockdown in vitro promoted ROS generation, BMSC apoptosis, and adipogenic differentiation while attenuating osteogenic differentiation in BMSCs. Mechanistically, it suggested that the expression of PGC1-α protein was increased with miR-130b-3p inhibitor treatment in osteoporosis under hyperlipidemia conditions to improve mitochondrial function. Collectively, CoQ10 alleviates hyperlipidemia-induced osteoporosis in ApoE-/- mice and regulates adipocyte-osteoblast lineage allocation. The possible underlying mechanism may involve the improvement of mitochondrial function by modulating the miR-130b-3p/PGC-1α pathway.

Farnesoid X receptor overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in nonalcoholic fatty liver disease.

Oxidative stress-mediated activation of inflammasome has a significant effect on the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Farnesoid X receptor (NR1H4, FXR) has been implicated in biological function and many diseases, including NAFLD. The regulatory effect of FXR on oxidative stress and whether this process is related with the activation of absent melanoma 2 (AIM2) inflammasome in NAFLD remain unclear. In the present research, we confirmed that FXR in the livers of steatosis patients is significantly reduced compared with normal liver tissue by using the Gene Expression Omnibus (GEO) database and a palmitic acid (PA) - mediated steatosis model in AML-12 cells. Under the premise of ensuring the same food intake as the control group, overexpression of FXR in mice attenuated HFD-mediated weight gain and liver steatosis, facilitated lipid metabolism, improved fatty acid ß-oxidation, lipolysis, and reduced fatty acid synthesis and intake, which also inhibited the activation of AIM2 inflammasome. Overexpression of FXR alleviated PA-induced triglyceride (TG) accumulation, imbalance of lipid homeostasis, and the activation of AIM2 inflammasome in hepatic steatosis cells, while FXR knockdown appeared the opposite effects. FXR overexpression suppressed PA- and HFD-induced oxidative stress, but FXR siRNA demonstrated the opposite influence. The decreased ROS generation may be the reason why FXR weakens AIM2 activation when a fatty acid overload occurs. In conclusion, our results confirm that other than regulating lipid homeostasis and blocking NLRP3 inflammasome activation, FXR improves hepatic steatosis by a novel mechanism that inhibits oxidative stress and AIM2 inflammasome activation.

Logistic analysis of the recurrence of laparoscopic percutaneous extraperitoneal repair of pediatric inguinal hernia: A report of 486 cases.

BACKGROUND: Although the laparoscopic treatment of pediatric inguinal hernia (PIH) has more benefits than traditional surgery, it is difficult to completely avoid the problem of recurrence. The aim of this study was to use a logistic regression model to investigate the causes of recurrence after laparoscopic percutaneous extraperitoneal repair (LPER) of PIH. PATIENTS AND METHODS: From June 2017 to December 2021, 486 cases of PIH were performed using LPER in our department. We utilized a two-port approach to implement LPER for PIH. All cases were followed up and the recurrent cases were recorded in detail. We used a logistic regression model to analyze the clinical data in order to find the reasons for recurrence. RESULTS: We completed 486 cases with an internal inguinal ostium high ligation using laparoscopic surgery without conversion. Patients were followed for 10-29 months with an average of 18.2 months and 8 cases had recurrent ipsilateral hernia, including 4 recurrent cases in 89 cases (4.49%) using absorbable suture, 1 in 7 cases (14.29%) with internal inguinal ostium larger than 25 mm, 2 in 26 cases (7.69%) with BMI greater than 21, 2 in 41 cases (4.88%) with postoperative chronic constipation. The total recurrence rate was 1.65%. A foreign body reaction occurred in 2 cases, there were no complications such as scrotal hematoma, trocar umbilical hernia and testicular atrophy, and no deaths in this study. Univariate logistic regression analysis showed that patient BMI, ligation suture, diameter of the internal inguinal ostium and postoperative chronic constipation were significant variables (P values 0.093, 0.027, 0.060 and 0.081). The multivariate logistic regression analysis showed that the ligation suture and the diameter of the internal inguinal ostium were the main risk factors for postoperative recurrence, the odds ratio (OR) value were 5.374 and 2.801, the P values 0.018 and 0.046, and the 95% CI were 2.513-11.642 and 1.134-9.125. The area under ROC curve (AUC) for the logistic regression model was 0.735 (the 95% CI 0.677-0.801, P < 0.01). CONCLUSION: An LPER for PIH is a safe and effective operation, but there still remains a small probability of recurrence. In order to reduce the recurrence rate of LPER, we should improve surgical skills, choose an appropriate ligature and avoid using LPER for a huge internal inguinal ostium (especially over 25 mm). It is appropriate to be converted to open surgery for the patients with a very wide internal inguinal ostium.

Epigenetic modification of TWIST1 in macrophages promotes hypertension-induced atherosclerotic plaque instability.

It is accepted that hypertension is a major, independent risk factor for atherosclerotic cardiovascular ischemic events, which are mainly attributed to the formation of unstable, vulnerable atherosclerotic lesions. But the mechanisms by which hypertension aggravates atherosclerosis (AS) through increased macrophage recruitment are unknown. It has been reported that TWIST1 can regulate the shear stress of blood flow in endothelial cells to promote the development of atherosclerosis, but the function of TWIST1 in macrophage recruitment during hypertension remains undefined. Here, the roles of TWIST1 in macrophage activation during N w -nitro-l-arginine-methyl ester (L-NAME; NO-synthase (NOS) inhibitor)-induced hypertension were investigated in ApoE-/- mice fed a high-fat diet (HFD) and RAW264.7 cells treated with oxidized low-density lipoprotein(ox-LDL). Oil Red O staining and hematoxylin and eosin staining were adopted to analyze atherosclerotic lesions and plaque instability. Chromatin immunoprecipitation (ChIP)-PCR was used to explore whether Lysine-specific histone demethylase 1A (LSD1/KDM1A) and Variegated suppressor 3-9 homolog 1 (SUV39H1) could regulate histone modification of the TWIST1 promoter. We reported that L-NAME increased the expression of TWIST1 in the aortic tissues of ApoE-/- mice fed a high-fat diet (HFD) and RAW264.7 cells treated with ox-LDL. TWIST1 accelerated the development of an unstable atherosclerotic phenotype by promoting macrophage activation, inflammatory factor secretion, macrophage polarization, and lipid phagocytosis. Moreover, we found that H3K9me2 and H3K9me3 in the TWIST1 promoter could be coregulated by LSD1 and SUV39H1, and this process was modulated by CK2α. Taken together, these results revealed that TWIST1 in macrophages is a critical factor that mediates foam cell formation and enhances atherosclerotic plaque vulnerability during hypertension, and targeting TWIST1 may be a promising new therapeutic approach for delaying the progression of AS in hypertension.

Restoration and preservation effects of mung bean antioxidant peptides on H2O2-induced WRL-68 cells via Keap1-Nrf2 pathway.

Mung bean antioxidant peptides (MBAPs) were prepared from mung bean protein hydrolysate, and four peptide sequences including Ser-Asp-Arg-Thr-Gln-Ala-Pro-His (~953 Da), Ser-His-Pro-Gly-Asp-Phe-Thr-Pro-Val (~956 Da), Ser-Asp-Arg-Trp-Phe (~710 Da), and Leu-Asp-Arg-Gln-Leu (~644 Da) were identified. The effects of MBAPs on the oxidation-induced normal human liver cell line WRL-68 were analyzed to determine the mechanism protecting the oxidation-induced injury. The results showed that the cells were subjected to certain oxidative damage by H2O2 induction, as evidenced by decreased cell number and viability, overproduction of intracellular ROS, and decreased mitochondrial membrane potential. Compared with the H2O2-induced group, the MBAP-treated oxidation-induced group exhibited significantly higher cell number and viability, and the intracellular ROS was similar to that of the control group, suggesting that MBAP scavenges excessive intracellular free radicals after acting on the oxidation-induced cells. Combined with Western blotting results, it was concluded that the MBAP-treated oxidation-induced group also significantly promoted the expression of proteins related to the kelch-like ech-related protein 1 (Keap1)/ nuclear factor e2-related factor 2 (Nrf2) signaling pathway, which resulted in an approximately 2-fold increase in antioxidant enzymes, and a decrease in malondialdehyde content of approximately 55% compared to oxidatively-induced cells, leading to the recovery of both cell morphology and viability. These results suggest that MBAPs scavenge intracellular free radicals and improve oxidative stress in hepatocytes through the expression of Keap1/Nrf2 pathway-related protein, thereby reducing oxidative attack on the liver. Therefore, MBAP is applied as a nutritional ingredient in the functional food field, and this study provides a theoretical basis for the high utilization of mung bean proteins.

Catalpol ameliorates dexamethasone-induced osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via the activation of PKD1 promoter.

OBJECTIVE: To investigate the effects of CA on glucocorticoid-induced osteoporosis (GIOP) and lucubrate the underlying mechanism of CA via the activation of polycystic kidney disease-1(PKD1) in bone marrow mesenchymal stem cells (BMSCs). METHODS: In vivo, a GIOP model in mice treated with dexamethasone (Dex) was established. Biomechanical, micro-CT, immunofluorescence staining of OCN, ALP and PKD1 and others were severally determined. qRT-PCR and Western blot methods were adopted to elucidate the particular mechanisms of CA on GIOP. In addition, BMSCs cultured in vitro were also induced by Dex to verify the effects of CA. Finally, siRNA and luciferase activity assays were performed to confirm the mechanisms. RESULTS: We found that CA could restore the destroyed bone microarchitecture and increase the bone mass in GIOP mice. CA could also upregulate PKD1 protein expression, reduce oxidative stress, and promote mRNA expression of bone formation-associated markers in GIOP mice. Furthermore, it was also observed that CA reduced oxidative stress and promoted osteogenic differentiation in Dex-induced BMSCs. Mechanically, CA could promote protein expression via increasing the activity of PKD1 promoter. CONCLUSION: This study provides important evidences for CA in the further clinical treatment of GIOP, reveals the activation of PKD1 promoter as the underlying mechanism.

The efficacy and safety assessment of oncolytic virotherapies in the treatment of advanced melanoma: a systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports. METHODS: Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies. RESULTS: Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy. CONCLUSION: Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.