Extracellular Vesicles Obtained From Lung Adenocarcinoma Cells Cultured Under Intermittent Hypoxia Induce M2 Macrophage Polarization via miR-20a-5p Delivery.

Conclusion: These findings indicate that EVs obtained from lung adenocarcinoma cells cultured under IH deliver miR-20a-5p to promote M2 macrophage polarization by targeting PTEN.

Research on the anti-aging efficacy of fermented lysate VHProbi® MixA as the functional skincare ingredient.

AIMS: This study aimed to investigate the efficacy of a cream containing VHProbi® MixA for improving skin aging. METHODS AND RESULTS: In vitro studies demonstrated that the lysate produced from Lacticaseibacillus paracasei E12 (E12) exhibited immunoregulatory effects in a 3D skin model, with significant reductions in levels of interleukin (IL)-1α, IL-1ß, and IL-8 (P < 0.05) compared with the control group. In addition, the lysate of E12 mitigated the hydrogen peroxide-induced mortality of 3D skin cells and enhanced the transepithelial electrical resistance to show significant differences in comparison with control (P < 0.05), suggesting favorable antioxidant effects. The antioxidant capacity of the lysate of E12 was also confirmed using the Caenorhabditis elegans N2 model. C. elegans N2 fed the E12 strain showed a significantly higher % survival than those fed Escherichia coli OP50 (P < 0.05). Subsequently, VHProbi® MixA was formulated using the fermented lysates of E12, Lactiplantibacillus plantarum E15, and Limosilactobacillus reuteri E18. In a clinical study to ascertain if a cream containing VHProbi® MixA could improve the skin aging trends, participants were asked to use the investigational products for 60 days, and six indicators, transepidermal water loss (TEWL), hydration, elasticity, wrinkles, skin texture (roughness), and pores were measured at baseline and the endpoint of the study. A self-evaluation questionnaire analysis was also provided. TEWL, wrinkles, skin texture, and thickness of pores decreased significantly after treatment with the cream for 60 days (P < 0.01), whereas hydration and elasticity increased significantly (P < 0.01), in comparison to the baseline measurements. CONCLUSIONS: We hypothesize that the use of the cream containing VHProbi® MixA could be favorable for skin anti-aging management.

Klotho inhibits the activation of NLRP3 inflammasome to alleviate lipopolysaccharide-induced inflammatory injury in A549 cells and restore mitochondrial function through SIRT1/Nrf2 signaling pathway.

Acute lung injury is a severe clinical condition constituting a major cause of mortality in intensive care units. This study aimed to investigate the role of klotho in alleviating lipopolysaccharide (LPS)-induced acute lung injury. LPS-induced acute lung injury was used to simulate the acute lung injury caused by severe pneumonia in vitro. The viability and apoptosis of A549 cells were detected by cell counting kit-8 assay and flow cytometry. The inflammatory response, oxidative stress, and mitochondrial function in A549 cells were analyzed by commercial assay kits and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining. The expression of apoptosis-related proteins, Sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins, and NOD-like receptor family pyrin domain containing 3 (NLRP3) expression in A549 cells was detected by western blot. The mtDNA synthase level in A549 cells was analyzed by reverse transcription-quantitative polymerase chain reaction. The results showed that, klotho had no cytotoxic effect on A549 cells. The viability and mitochondrial function were inhibited and apoptosis, inflammatory response, and oxidative stress were aggravated in LPS-induced A549 cells, which were all reversed by klotho. Klotho activated the SIRT1/Nrf2 signaling pathway to inhibit the LPS-induced NLRP3 inflammasome activation in A549 cells. However, EX527, a SIRT1 inhibitor, attenuated the klotho effect to suppress viability and mitochondrial function and promoted apoptosis, inflammatory response, and oxidative stress of A549 cells. In conclusion, klotho inhibited the activation of NLRP3 inflammasome to alleviate LPS-induced inflammatory injury of A549 cells and restore mitochondrial function through activating the SIRT1/Nrf2 signaling pathway.

Effects of a lotion containing probiotic ferment lysate as the main functional ingredient on enhancing skin barrier: a randomized, self-control study.

There is an emergent need to develop functional cosmetic ingredients for the topical management of skin barrier function. This study aimed to investigate the efficacy of a lotion containing fermented lysates VHProbi® Mix R for enhancing the skin barrier. In vitro studies demonstrated that fermented cultures of both Lacticaseibacillus rhamnosus VHProbi® E06 (E06) and L. paracasei VHProbi® E12 (E12) had antioxidant capacity, showing promising scavenging capability for 2,2-diphenyl-1-picryl-hydrazyl. The antioxidant capacity of these strains was also demonstrated in the model of Caenorhabditis elegans. In addition, the fermented lysates of both E06 and E12 enhanced the proliferation of HaCaT cells and ameliorated the toxicity induced by Staphylococcus aureus ATCC 25923, hydrogen peroxide, and ultraviolet B radiation in the HaCaT cell models, which simulated the irritants that facial sensitive skin is exposed to. Subsequently, the ingredient VHProbi® Mix R was formulated using four kinds of fermented lysates: E06, E12, Lactiplantibacillus plantarum VHProbi® E15, and Lactobacillus helveticus VHProbi® Y21. A clinical study was conducted to investigate whether a lotion containing VHProbi® Mix R would be beneficial for people to enhance skin barrier. The participants were asked to use the investigational product for 30 days. Several indicators, including transepidermal water loss (TEWL), skin moisturization, and redness were measured at day 0 and day 30 using VISIA®-CR and CK®-MPA systems. Meanwhile, the burden of sensitive skin (BoSS) and self-assessment questionnaires were performed at baseline and endpoint of this study. The study data showed that at day 30, there was a significant decrease in TEWL (P < 0.01), redness measured by CK®-MPA (P < 0.01), and redness profile measured by VISIA®-CR compared with the baseline measurements. Skin moisturization had significantly increased after treatment with the lotion for 30 days. BoSS and self-assessment questionnaires also substantiated that the participants felt a markedly positive change in their sensitive skin. Hence, we hypothesize that applying the topical functional VHProbi® Mix R could confer effective benefits for people with sensitive skin and this represents a promising intervention for enhancing skin barrier.

Features of osteoporosis in male patients with bronchiectasis, a cross-sectional study.

Background: Osteoporosis increases the burden and disease related adverse events of comorbidities in some chronic disease. The relationships between osteoporosis and bronchiectasis are not fully understood. This cross-sectional study explores the features of osteoporosis in male patients with bronchiectasis. Methods: From January 2017 to December 2019, male patients (age >50 years) with stable bronchiectasis were included, as were normal subjects. Data on demographic characteristics and clinical features were collected. Results: Totally, 108 male patients with bronchiectasis and 56 controls were analyzed. Osteoporosis was observed in 31.5% (34/108) of patients with bronchiectasis and 17.9% (10/56) of controls (P=0.001). The T-score negatively correlated with age (R=-0.235, P=0.014) and bronchiectasis severity index score (BSI; R=-0.336, P<0.001). BSI score ≥9 was a major factor associated with osteoporosis [odd ratio (OR) =4.52; 95% confidence interval (CI): 1.57-12.96; P=0.005]. Other factors associated with osteoporosis included body-mass index (BMI) <18.5 kg/m2 (OR =3.44; 95% CI: 1.13-10.46; P=0.030), age ≥65 years (OR =2.87; 95% CI: 1.01-7.55; P=0.033), and a smoking history (OR =2.78; 95% CI: 1.04-7.47; P=0.042). Conclusions: The prevalence of osteoporosis was higher in male bronchiectasis patients than that in controls. Factors including age, BMI, smoking history, and BSI were associated with osteoporosis. Early diagnosis and treatment might be of great value in prevention and management of osteoporosis in patients with bronchiectasis.

A pilot study on the efficacy of topical lotion containing anti-acne postbiotic in subjects with mild -to -moderate acne.

Introduction: Acne can compromise facial esthetics and become a mental burden, especially when it occurs in puberty. Skincare cosmetics with anti-acne efficiency is more convenient than other treatment modalities, such as dietary supplements, in certain circumstances. The purpose of this study was to investigate the efficacy of an anti-acne lotion in alleviating acne. Methods: In our study, an anti-acne lotion containing ferment lysate produced by Lactiplantibacillus plantarum VHProbi® E15 were applied to subjects with mild -to -moderate acne over 4 weeks. The efficacy was evaluated based on instrumental measurements using Visia®-CR and CK-MPA® system. Results and discussion: The anti-acne lotion exhibited favorable safety, meeting the stringent criteria for the detection of microbes, heavy metals, toxicity, and irritation. After 2 weeks of treatment, a statistically significant improvement in acne lesions was observed compared to baseline (P < 0.01), and this continued to the end of the study. After 4 weeks of treatment, the transepidermal water loss (P < 0.05) and sebum production (P < 0.05) were significantly decreased in subjects compared to baseline. In addition, the pore/area of interest (AOI) and stratum corneum hydration displayed slightly positive changes throughout treatment. Thus, we conclude that applying topical anti-acne lotion may be safe and confer effective benefits in people with mild -to -moderate acne and represents a promising therapeutic option for acne.

Positive effect of Bifidobacterium animalis subsp. lactis VHProbi YB11 in improving gastrointestinal movement of mice having constipation.

Introduction: The aim of this study was to investigate the effects of Bifidobacterium animalis subsp. lactis VHProbi® YB11 (YB11) on attenuating sucralfate-induced constipation in BALB/c mice. The strain of YB11 exhibited favorable tolerance of simulated gastrointestinal (GI) juice. Only 0.42 Log value declined when the live cells of YB11 were co-incubated with simulated GI juice. Meanwhile, this strain also displayed perfect ability to adhere the intestinal epithelium Caco-2 cells with adhesion index of 18.5. 24 of female mice were randomized into four groups. Methods: The normal group (NOR) was fed with a normal diet, whereas the placebo group (PLA), positive group (POS), and probiotic group (PRO) were fed with sucralfate to induce constipation. After first successfully establishing the constipation model, groups NOR and PLA received the oral administration of saline solutions. Meanwhile, the POS and PRO groups were orally administered phenolphthalein and YB11 suspensions, respectively. Several indices, including fecal water content, GI transit time, short-chain fatty acids (SCFAs), intestinal neuropeptides level, and histopathology of colonic tissues, were investigated. Results and Discussion: Compared with PLA, YB11 had a positive effect in increasing the fecal water content and intestinal peristalsis. Some positive trends, including the acetic and total acids level of fecal samples, and the colonic tissue histopathology, were also observed. Furthermore, YB11 had an ability to upregulate the levels of gut excitatory neuropeptides including motilin, gastrin, and substance P, whereas it downregulated the levels of inhibitory neuropeptides including endothelin-1, somatostatin, and vasoactive intestinal peptide. We conclude that the strain YB11 has a positive impact on improving gastrointestinal mobility and reducing the severity of constipation.

Development of Novel Topical Anti-Acne Cream Containing Postbiotics for Mild-to-Moderate Acne: An Observational Study to Evaluate Its Efficacy.

Background: Acne is one of the most common skin diseases in adolescents and results in high healthcare costs and psychological burdens severely affecting individuals. Treatments other than contraceptives, antibiotics, and photodynamic therapies are needed to prevent and/or improve acne's onset and evolution. Aims: The purpose of this study was to investigate the efficacy of a fermentation lysate of Lactiplantibacillus plantarum VHProbi® V22 in ameliorating acne. Methods: An anti-acne skincare cream containing fermentation culture lysate was applied to subjects with mild-to-moderate acne vulgaris for 4 weeks. The assessments were evaluated based on instrumental measurements using Visia®-CR and CK-MPA® systems. Results and Conclusions: The anti-acne skincare cream was found to be safe and not cause any irritation. Significant improvements in the acne lesion proportion (P < 0.01), transepidermal water loss (P < 0.001), and sebum secretion (P < 0.05) were observed in comparison to the baseline in the subjects. The analysis of the statistical data after 4 weeks of treatment showed a positive decrease in skin tone, stratum corneum hydration, and superficial pH without statistical significance, compared with the baseline. The results of this study suggest that the topical application of the anti-acne skincare cream was effective and safe in subjects with mild-to-moderate acne and could represent an optional complement for acne treatments.

No Evidence of Re-infection or Person-to-Person Transmission in Cured COVID-19 Patients in Guangzhou, a Retrospective Observational Study.

Objectives: To clarify the clinical characteristics of cured patients with coronavirus disease (COVID-19), and to clarify the re-infection and person-to-person transmission in the cured. Methods: A total of 187 cured COVID-19 patients with antibody test were followed up every 2 weeks in this retrospective observational study. Assessment for general condition, symptoms, epidemiological contact history, polymerase chain reaction (PCR) assay, and antibody tests were performed and recorded. Information from Guangzhou CDC was also screened. Results: There were 33 (17.6%) patients with negative results for IgG and 35 (18.7%) patients with positive results for IgM. The average days of antibody detection from disease onset were 53.0. PCR assay was positive in 10 (5.3%) patients during the follow-up. Neither IgG nor IgM results showed a relationship with PCR test results (all P > 0.05). Neither re-infection nor person-to-person transmission was found in the cured patients. Factors associated with appearance of antibody comprised hospitalization days (OR: 1.06, 95%CI: 1.02-1.11, P = 0.006) and antibiotics treatment (OR: 3.50, 95%CI: 1.40-8.77, P = 0.007). Conclusions: In our study, no evidence of person-to-person transmission was found in cured COVID-19 patients. There seemed to be no re-infection in the cured COVID-19 patients in Guangzhou. These finding suggest that the cured do not cause the spread of disease. Additionally, neither IgG nor IgM can be used to replace the PCR test in cured patients.

Trihexyphenidyl induced malignant hyperthermia in a patient with Parkinson's disease complicated with pneumonia: A case report.

INTRODUCTION: Drug-induced fever is easy to overlook in respiratory departments. High fever is a rare side effect of trihexyphenidyl, which can be used clinically to treat Parkinson's disease. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a group of clinical syndromes caused by various diseases, resulting in water retention and refractory hyponatremia. However, pneumonia combined with malignant hyperthermia and SIADH has rarely been reported. We describe an unusual case of malignant hyperthermia and refractory hyponatremia due to trihexyphenidyl adverse reaction. PATIENT CONCERNS: Fifty-five-year-old male with pneumonia presented with malignant hyperthermia and refractory hyponatremia has a history of Parkinson's disease. DIAGNOSIS: Early considerations related the described hyperthermia findings to the manifestations of pneumonia. However, the last findings were due to trihexyphenidyl adverse reaction. INTERVENTIONS: Broad-spectrum antibiotics, oral and intravenous supplement of concentrated sodium chloride, drug, and physical cooling. OUTCOMES: The patient survived. During the 3-month follow up, the patient was no recurrence of fever or hyponatremia. CONCLUSION: High fever and SIADH can be a rare adverse reaction to trihexyphenidyl. Therefore, possible drug factors should be considered in the case. Consideration of other possible causes can improve early diagnosis and treatment of patients with fever of unknown origins.

Effect of gene-gene and gene-environment interaction on the risk of first-ever stroke and poststroke death.

BACKGROUND: Multiple genetic and environmental factors contribute to the individual-level heterogeneity in stroke. This study aimed to assess how the genetic interactions confer risk of stroke. METHODS: In a Chinese case-control study including 1,405 strokes and 1,263 controls who were followed up (range, 0.1-6.0 years), eight genes, including apolipoprotein(a) (APOA1), methylenetetrahydrofolate reductase (MTHFR), vitamin K epoxide reductase complex subunit 1 (VKORC1), arachidonate 5-lipoxygenase-activating protein (ALOX5AP), NOTCH3, chromosome 9p21.3(Chr.9p21.3), vascular endothelial growth factor (VEGFA), and kinase insert domain-containing receptor (KDR), were analyzed for interactions by the generalized multifactor dimensionality reduction method and validated by the multivariate logistic regression models. The genetic associations with carotid artery intima-media thickness (IMT) were examined. RESULTS: The interaction of VKORC1 and Chr.9p21.3 was identified for stroke and its worse prognosis, and subjects having the VKORC1 rs2359612C and Chr.9p21.3 rs10757274G alleles had higher risks for stroke (OR = 1.83, 95% CI = 1.32-2.52) as well as for stroke recurrence (HR = 1.84, 95% CI = 1.24-2.73), cardiovascular events (HR = 1.65, 95% CI = 1.15-2.38), and cardiovascular mortality (HR = 2.16, 95% CI = 1.24-3.79). Supporting, they were associated with higher IMT. Hypertension or physical inactivity increased the risk effect. The interaction of VEGFA rs833061C and KDR rs2305948T was identified for hemorrhagic stroke. CONCLUSIONS: Our findings identified two novel genetic interactions of VKORC1 and Chr.9p21.3 and of VEGFA and KDR for risk of stroke and subtypes as well as future stroke prognosis.

MicroRNA-216a promotes M1 macrophages polarization and atherosclerosis progression by activating telomerase via the Smad3/NF-κB pathway.

Macrophages exhibit heterogeneity and plasticity and imbalance between pro-inflammatory and anti-inflammatory macrophages plays a critical role in atherosclerosis progression. Telomerase reverse transcriptase (TERT) in macrophages can be activated by nuclear factor-kappa B (NF-κB), but the regulation of telomerase activation on macrophages polarization remains unknown. We previously identified microRNA-216a (miR-216a) to promote inflammation through directly targeting the Smad3/NF-κB pathway. The present study aimed to assess whether miR-216a can regulate telomerase activity and promote macrophages polarization during atherosclerosis progression. The results verified that TERT was highly expressed in macrophages of human carotid atherosclerotic plaques. miR-216a was found to promote telomerase activation in macrophages by 4.5-fold (P = 0.002) through the Smad3/NF-κB pathway. miR-216a also induced macrophages senescence characterized by senescence-associated-ß-galactosidase activity and p53 and p16 expression. TERT overexpression promoted the transformation of M2 to M1 while this conversion was suppressed once TERT was inhibited, and the related inflammatory factors and lipid uptake ability of M1 cells were also increased by TERT. In the carotid atherosclerotic plaques from miR-216a-treated apolipoprotein E-/- mice, the numbers of M1 macrophages were increased whereas M2 cells reduced, accompanying with inhibited Smad3 expression and upregulated inflammatory markers and TERT activity. Furthermore, plasma miR-216a level was specifically higher in patients with vulnerable mixed plaques (n = 181) than those with calcified plaques (n = 73) and controls (n = 264). In summary, our findings first revealed a new molecular mechanism of macrophage polarization involving telomerase activation induced by miR-216a through the Smad3/NF-κB signaling, which might serve as a potential therapeutic target for atherosclerosis progression.

MicroRNA-216a induces endothelial senescence and inflammation via Smad3/IκBα pathway.

Vascular endothelial senescence contributes to atherosclerosis and coronary artery disease (CAD), but the mechanisms are yet to be clarified. We identified that microRNA-216a (miR-216a) significantly increased in senescent endothelial cells. The replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established to explore the role of miR-216a in endothelial ageing and dysfunction. Luciferase assay indicated that Smad3 was a direct target of miR-216a. Stable expression of miR-216a induced a premature senescence-like phenotype in HUVECs with an impairment in proliferation and migration and led to an increased adhesion to monocytes by inhibiting Smad3 expression and thereafter modulating the degradation of NF-κB inhibitor alpha (IκBα) and activation of adhesion molecules. Conversely, inhibition of endogenous miR-216a in senescent HUVECs rescued Smad3 and IκBα expression and inhibited monocytes attachment. Plasma miR-216a was significantly higher in old CAD patients (>50 years) and associated with increased 31% risk for CAD (odds ratio 1.31, 95% confidence interval 1.03-1.66; P = .03) compared with the matched healthy controls (>50 years). Taken together, our data suggested that miR-216a promotes endothelial senescence and inflammation as an endogenous inhibitor of Smad3/IκBα pathway, which might serve as a novel target for ageing-related atherosclerotic diseases.

The association of telomere attrition with first-onset stroke in Southern Chinese: a case-control study and meta-analysis.

The relationship between telomere length and stroke was inconsistent mostly due to different pathogenesis of subtypes, environment and genetics. We aimed to assess whether leukocyte telomere contributes to stroke in Southern Chinese by investigating a case-control study comprising 543 cases (224 atherothrombotic stroke, 94 hemorrhagic stroke and 225 lacunar infraction) and 616 controls and replicated the investigation in an independent study comprising 773 cases and 875 controls with the same diagnostic criteria. Telomere was inversely correlated with increasing age in controls (correlation coefficient γ = -0.28, P < 0.001) and in cases with atherothrombotic stroke (γ = -0.17, P = 0.012). Individuals within the lowest tertile of telomere showed a higher risk for atherothrombotic stroke [odds ratio 2.33, 95% confidence (CI) 1.42-3.83; P = 0.003], whereas had a lower presence of lacunar infarction (OR 0.49, 95% CI 0.30-0.81; P = 0.007). Similar results were obtained in the second replication study. A further meta-analysis showed a 12% increased pooled risk of ischemic stroke (95% CI 1.04-1.18) in relation to shorter telomere, but this association was stronger in the retrospective studies and in Asians when stratified by study design and ethnicity. Our data provided the first evidence that in Southern Chinese stroke population, leukocyte telomere is independently associated with atherothrombotic stroke and lacunar infarction.