Soyghurt Potentially Controls the Level of sFlt1 and PLGF in Preeclampsia Maternal Serum-Induced Placental Trophoblast Cell in vitro.

Purpose: To observe the effect of soya yoghurt (Soyghurt), which is high in flavonoid substance, on the expression of preeclampsia biomarkers (sFLT-1 and PLGF) on preeclampsia serum-induced trophoblast primary cell culture isolated from placental tissue. Methods: The trophoblast primary culture was induced by preeclampsia serum (10%). The Soyghurt treatment was performed with 2.5%, 5%, and 7.5% Soyghurt supernatant concentrations in culture media. The expression of preeclampsia markers, sFLT-1 and PLGF, were evaluated using ELISA. Results: Expression of sFLT-1 on preeclampsia-induced cell culture treated with Soyghurt was significantly lowered compared to the untreated group (p<0.01). However, no significant difference was observed in the PLGF levels of all groups induced by preeclampsia serum (p>0.05). Conclusion: This study demonstrates the potential effect of Soyghurt's in balancing preeclampsia marker expression by inhibiting the expression of sFLT-1 in preeclampsia serum -induced trophoblast cells.

Progress in the Development of Stem Cell-Derived Cell-Free Therapies for Skin Aging.

Introduction: The skin is a vital organ as the body's largest barrier, but its function declines with aging. Therefore, research into effective regeneration treatments must continue to advance. Stem cell transplantation, a cell-based therapy, has become a popular skin-aging treatment, although it comes with drawbacks like host immune reactions. Stem cell-derived cell-free therapies have emerged as an alternative, backed by promising preclinical findings. Stem cell secretomes and extracellular vesicles (EVs) are the key components in cell-free therapy from stem cells. However, comprehensive reviews on the mechanisms of such treatments for skin aging are still limited. Purpose: This review discusses stem cell-derived cell-free therapy's potential mechanisms of action related to skin aging prevention by identifying specific molecular targets suitable for the interventions. Methods: A search identified 27 relevant in vitro studies on stem cell-derived cell-free therapy interventions in skin aging model cells without restricting publication years using PubMed, Scopus, and Google Scholar. Results: Stem cell-derived cell-free therapy can prevent skin aging through various mechanisms, such as (1) involvement of multiple regenerative pathways [NFkb, AP-1, MAPK, P-AKT, NRF2, SIRT-1]; (2) oxidative stress regulation [by reducing oxidants (HO-1, NQO1) and enhancing antioxidants (SOD1, CAT, GP, FRAP)]; (3) preventing ECM degradation [by increasing elastin, collagen, HA, TIMP, and reducing MMP]; (4) regulating cell activity [by reducing cell senescence (SA-ß-gal), apoptosis, and cell cycle arrest (P53, P12, P16); and enhancing autophagy, cell migration, and cell proliferation (Ki67)] (5) Regulating the inflammatory pathway [by reducing IL-6, IL-1, TNF-⍺, and increasing TGF-ß]. Several clinical trials have also revealed improvements in wrinkles, elasticity, hydration, pores, and pigmentation. Conclusion: Stem cell-derived cell-free therapy is a potential novel treatment for skin aging by cell rejuvenation through various molecular mechanisms.

Anthocyanin-Containing Purple Sweet Potato (Ipomoea batatas L.) Synbiotic Yogurt Inhibited 3T3-L1 Adipogenesis by Suppressing White Adipocyte-Specific Genes.

Purpose: We unravel the effect of anthocyanin-containing purple sweet potato synbiotic yogurt (PSPY) on 3T3-L1 adipocyte differentiation and its fundamental molecular mechanisms. Methods: Molecular docking simulation was performed to observe and identify the affinity and interaction between bioactive compounds and targeted proteins. MDI (isobutylmethylxanthine, dexamethasone, and insulin)-containing medium, a cocktail that stimulates adipogenesis, was used in this study. The toxic effect possibility of the yogurt product was evaluated using 3-[4, 5-dimethylthiazol-2-yl]-2.5 diphenyl tetrazolium bromide (MTT) assay. A 0.25%, 0.5%, 1%, and 5% (v/v) plain or purple sweet potato yogurt supernatant was given to 3T3-L1 preadipocyte culture medium from 24 h after seeding until day 11 of MDI-induced differentiation. The mRNA expression and lipid accumulation were analyzed using RT-qPCR and Oil red O staining, respectively, on day 11 after differentiation induction. Results: In silico study suggested that anthocyanin-derived compounds have the potential to inhibit peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator for white adipogenesis. Anthocyanin-containing PSPY significantly suppressed the expression of Pparg, Adipoq, Slc2a4, and Pgc1a. PSPY significantly suppressed Pparg with 1% and 5% concentrations, while with a concentration of 0.25%, PSPY significantly suppressed Adipoq expression as compared to control. Significant inhibition of Slc2a4 and Pgc1a was observed starting from a 0.25% concentration of PSPY. The suppression of adipogenic genes was also observed with the treatment of plain yogurt; however, the effects were relatively lower than the PSPY. The group treated with 1% and 5% of PSPY also showed inhibition effects on lipid accumulation. Conclusion: This study demonstrated PSPY inhibition effect on white adipocyte differentiation through suppression of Pparg and its downstream genes, Adipoq and Slc2a4, indicating the potential of this yogurt as a functional food for obesity management and prevention.

The association between serum hypoxia inducible factor-1α level and urothelial bladder cancer: A preliminary study.

INTRODUCTION: We aim to evaluate the association between serum hypoxia inducible factor (HIF)-1α level and stage and grade of urothelial bladder cancer (UBC). METHODS: A case-control study was conducted at Haji Adam Malik Hospital Medan, Indonesia. Inclusion criteria for case group was subject aged 18 years or older and diagnosed with UBC based on histopathological examination. Control group consisted of gender and age matched healthy subjects. Serum HIF-1α level was determined using ELISA method. Data was analyzed with chi square, Mann Whitney, and independent T tests. RESULTS: A total of 80 subjects were enrolled and divided into case and control groups equally. Most subjects were males with mean age of 69.65 years for case group and 68.25 years for control group. Most subjects had advanced primary tumor and lymph node stages. Only 30% subjects had metastasized UBC. Higher serum HIF-1α level was observed in case group (p < 0.001). Serum HIF-1α level was strongly associated with metastasis stage (p < 0.001), followed by lymph node (p = 0.005) and primary tumor (p = 0. 013) stages. Serum HIF-1α level was not associated with grading (p = 0.134). CONCLUSIONS: Serum HIF-1α level is associated with staging but not grading of UBC.

Differences in endosomal Rab gene expression between positive and negative COVID-19 patients.

OBJECTIVE: SARS CoV-2, the etiologic agent of coronavirus disease-2019 (COVID-19) is well-known to use ACE2 to begin internalization. Some viruses enter the host cell through the endocytosis process and involve some endocytosis proteins, such as the Rab family. However, the relationship between SARS CoV-2 infection with endocytic mRNA RAB5, RAB7, and RAB11B is unknown. This study aims to compare the expression of RAB5, RAB7, and RAB11B between positive and negative COVID-19 patient groups. RESULTS: Both viral and human epithelial RNA Isolation and RT-PCR were performed from 249 samples. The genes expression was analysed using appropriate statistical tests. We found the Median (inter-quartile range/IQR) of RAB5, RAB7, and RAB11B expression among the COVID-19 patient group was 2.99 (1.88), 0.17 (0.47), 0.47 (1.49), and 1.60 (2.88), 1.05 (2.49), 1.10 (3.96) among control group respectively. We proceeded with Mann Whitney U Test and found that RAB5 expression was significantly increased (P < 0.001), and RAB7 and RAB11B expression was significantly decreased (P < 0.001 and P = 0.036) in the COVID-19 patient group compared to the control group. This first report showed significant differences in RAB5, RAB7, and RAB11B exist between COVID-19 positive and negative patients.

Acute and sub-chronic oral toxicity study of purple sweet potato (Ipomoea batatas [L.] Lam) yogurt in mice (Mus musculus).

Background and Aim: Food safety is an important aspect to be evaluated in preventing any potentially harmful side effects of food product such as yogurt. The purple sweet potato yogurt product was developed to combine the benefits of probiotic activities in yogurt and the bioactive effects of anthocyanin in purple sweet potato. This study was performed to investigate acute and sub-chronic oral toxicity of purple sweet potato yogurt (PSPY) in mice. Materials and Methods: Acute oral toxicity was evaluated by a 14-day observation for any clinical sign of toxicity on fifteen female balb/c mice following a single dosage of PSPY (nil, 2 or 5 g/kg body weight). The sub-chronic oral toxicity study was conducted by feeding PSPY to four groups of mice with the dose of 0, 12, 20, and 40 g/kg body weight for 28 days, and another group of mice receiving 40 g/kg body weight purple sweet potato for 14 days longer to observe any delayed toxicity effect. Body weight and clinical signs of toxicity were observed daily. Liver and kidney macroscopy and relative organ weight, liver histology, liver enzyme, and hematology profile analyses were done at the end of the study. Results: There were no signs of toxicity observed from the acute toxicity study and no abnormality in body weight, relative organ weight, and gross organ examination. In the sub-chronic toxicity study, there were no clinical signs of toxicity, no significant differences in body weight, relative liver weight, liver enzymes, hematology profile, or abnormality in gross and histological examination of the liver. Conclusion: This study shows that oral administration of PSPY in mice up to 5 g/kg body weight did not result in acute toxicity, while the dosage up to 40 g/kg body weight did not lead to sub-chronic toxicity.

Correlation of Knowledge, Attitude, and Practice Toward Probiotics for the Digestive System Among Health Science Students.

BACKGROUND: Probiotics have numerous health benefits to the digestive system, one of them being clinically able to prevent and treat diarrhea. The growing scientific evidence of probiotic benefits has led to increased production of probiotic products. Health science students, as future healthcare professionals (HCPs), should have more knowledge about probiotics to be able to give the right recommendation to their future patients and the larger community. This study aims to assess the knowledge, attitude, and practice towards probiotics of health science students in Universitas Padjadjaran, Indonesia. METHODS: A cross-sectional study was conducted on 87 students from Medical Studies, Midwifery, Pharmacy, and Nursing majors in 2020. Proportional cluster random sampling was used to select the study subjects, and an online survey was used to collect the data. Final data were exported to statistics software for analysis. Scores of each variable were categorized. Kruskal-Wallis test was used to analyze the statistical differences among the four groups. Spearman's rank correlation coefficient was used to analyze the relationship between knowledge, attitude, and practice variables. RESULTS: Of all respondents, 80% had adequate knowledge. More than half (52.9%) had a positive attitude, and most (62.1%) had a positive practice. There were significant correlations between knowledge-attitude and attitude-practice variables. Most respondents gained information on probiotics from the Internet (26%) and their lecturer (24%). P-value from Kruskal-Wallis test for knowledge, attitude, and practice are 0.466, 0.801, and 0.324, respectively. CONCLUSION: Most respondents had an adequate level of knowledge, a positive attitude, and a positive practice towards probiotics. Incorporating scientific evidence regarding probiotics from various studies into all health science majors' academic curricula and media may help equip the students with a better understanding of probiotics, therefore improving probiotics usage to prevent and treat digestive system diseases in the future.

Low Dose of ß-Carotene Regulates Inflammation, Reduces Caspase Signaling, and Correlates with Autophagy Activation in Cardiomyoblast Cell Lines.

BACKGROUND Excessive reactive oxygen species (ROS) stimulate mitochondrial damage that causes degenerative diseases such as cardiovascular disease (CVD). ß-carotene (BC), a natural antioxidant able to counteract free radicals, acts as a cytoprotective agent. However, knowledge of the role of BC on cardiomyoblasts is limited. In this study, we explored its role on COX4, Tom20, Nfr1, Nrf2, Nf-kappaB, LC3, p62, caspase 3, and caspase 9 and its association with cardiomyoblast viability and survival. MATERIAL AND METHODS H9C2 cell lines were seeded, cultivated until 90% to 100% confluency, and treated with various doses of BC: 10 µM, 1 µM, 0.1 µM, and 0.01 µM. After 24 h, the cells were harvested, lyzed, and tested for specific related protein expressions from each dose. RESULTS Low-dose BC induced autophagy most effectively at 1 µM, 0.1 µM, and 0.01 µM, as indicated by a decrease of LC3II and p62 levels. We observed that Nf-kB protein levels were suppressed; Nrf2 was stimulated, but Nrf1 was not altered significantly. Further, low-dose BC might stimulate cell viability by reducing apoptotic signals of caspase 3 and 9. Notably, low-dose BC also showed potential to increase Tom20 protein levels. CONCLUSIONS Low-dose BC supplementation shows beneficial effects, especially at 0.01 µM, by reducing inflammation through the suppression of Nf-kappaB and increase of Nrf2 level. Autophagy as a cellular maintenance mechanism was also stimulated, and the amount of the mitochondria marker Tom20 increased. Taken together, results showed that specific low-dose BC is effective and might improve cell viability by stimulating autophagy, inhibiting proinflammatory factors, and suppressing apoptosis.

Traditional Herbal Medicine Candidates as Complementary Treatments for COVID-19: A Review of Their Mechanisms, Pros and Cons.

Coronavirus disease 2019 (COVID-19) is a new infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that belongs to the coronavirus family. The first case was reported in December 2019, and the disease has become a pandemic. Impaired immune regulation is one of the factors that play a role in its pathogenesis and results in poor outcomes of COVID-19 patients. There have been many studies with drug candidates used as antivirals or immunomodulators. However, the results of these investigations showed that the drug candidates were not significantly effective against the disease. Meanwhile, people believe that consuming herbal immunomodulators can prevent or even cure COVID-19. Unfortunately, specific preclinical and clinical trials to evaluate the effects of herbal immunoregulators have not been conducted. Certain natural compounds might be effective for the treatment of COVID-19 based on general concepts from previous experiments. This review discusses some herbal agents extracted from various plants, including Echinacea, Cinchona, Curcuma longa, and Curcuma xanthorrhiza, which are considered for the treatment of COVID-19. In addition, we discuss the pros and cons of utilising herbal medicine during the COVID-19 pandemic, draw some conclusions, and make recommendations at the end of the session.

Tranexamic Acid Cream Protects Ultraviolet B-induced Photoaging in Balb/c Mice Skin by Increasing Mitochondrial Markers: Changes Lead to Improvement of Histological Appearance.

Tranexamic acid (TSA) is widely used as an antiaging treatment for reducing melasma and wrinkles. There are various mechanisms for wrinkle formation, and one of them is due to damage of the mitochondria. Research on mitochondria in the skin is very limited, so we are interested to see the changes that occur after application of TSA cream. We explored the effect of TSA on mitochondrial protein levels (PGC1α, Tom20, COX IV), which had affected to skin histological structure. Thirty male, 6-week-old, Balb/C mice were divided into five groups (negative control, positive control, TSA 3%, TSA 4% and TSA 5%). After 10 days of acclimatization, four groups of mice were exposed to UVB light, of which three groups were given TSA cream for 10 weeks. The skin tissue was excised for protein and histological studies. H&E staining was performed for evaluating histological changes in epidermal thickness and dermal elastosis. TSA treatment on the mice skin increased mitochondrial marker levels and epidermal thickness while decreasing dermal elastosis for all the treatment groups. Topical application of TSA significantly increased mitochondrial biogenesis which may cause alteration in epidermal thickness and reduced dermal elastosis in the histology of mice skin.

Filamentous structures in skeletal muscle: anchors for the subsarcolemmal space.

In skeletal muscle fibers, intermediate filaments and actin filaments provide structural support to the myofibrils and the sarcolemma. For many years, it was poorly understood from ultrastructural observations that how these filamentous structures were kept anchored. The present study was conducted to determine the architecture of filamentous anchoring structures in the subsarcolemmal space and the intermyofibrils. The diaphragms (Dp) of adult wild type and mdx mice (mdx is a model for Duchenne muscular dystrophy) were subjected to tension applied perpendicular to the long axis of the muscle fibers, with or without treatment with 1% Triton X-100 or 0.03% saponin. These experiments were conducted to confirm the presence and integrity of the filamentous anchoring structures. Transmission electron microscopy revealed that these structures provide firm transverse connections between the sarcolemma and peripheral myofibrils. Most of the filamentous structures appeared to be inserted into subsarcolemmal densities, forming anchoring connections between the sarcolemma and peripheral myofibrils. In some cases, actin filaments were found to run longitudinally in the subsarcolemmal space to connect to the sarcolemma or in some cases to connect to the intermyofibrils as elongated thin filaments. These filamentous anchoring structures were less common in the mdx Dp. Our data suggest that the transverse and longitudinal filamentous structures form an anchoring system in the subsarcolemmal space and the intermyofibrils.

Vesicular transport system in myotubes: ultrastructural study and signposting with vesicle-associated membrane proteins.

Myofibers have characteristic membrane compartments in their cytoplasm and sarcolemma, such as the sarcoplasmic reticulum, T-tubules, neuromuscular junction, and myotendinous junction. Little is known about the vesicular transport that is believed to mediate the development of these membrane compartments. We determined the locations of organelles in differentiating myotubes. Electron microscopic observation of a whole myotube revealed the arrangement of Golgi apparatus, rough endoplasmic reticulum, autolysosomes, mitochondria, and smooth endoplasmic reticulum from the perinuclear region toward the end of myotubes and the existence of a large number of vesicles near the ends of myotubes. Vesicles in myotubes were further characterized using immunofluorescence microscopy to analyze expression and localization of vesicle-associated membrane proteins (VAMPs). VAMPs are a family of seven proteins that regulate post-Golgi vesicular transport via the fusion of vesicles to the target membranes. Myotubes express five VAMPs in total. Vesicles with VAMP2, VAMP3, or VAMP5 were found near the ends of the myotubes. Some of these vesicles are also positive for caveolin-3, suggesting their participation in the development of T-tubules. Our morphological analyses revealed the characteristic arrangement of organelles in myotubes and the existence of transport vesicles near the ends of the myotubes.

The localization of VAMP5 in skeletal and cardiac muscle.

Vesicle-associated membrane protein 5 (VAMP5) is a member of the SNARE protein family, which is generally thought to regulate the docking and fusion of vesicles with their target membranes. This study investigated the expression and localization of the VAMP5 protein. Immunoblotting analyses detected the VAMP5 protein in skeletal muscle, heart, spleen, lung, liver, and kidney tissue, but not in brain or small intestine tissue. Through the immunofluorescence microscopy of skeletal muscle, we found that the expression level of VAMP5 varies among fibers. Most of the fibers with high expression levels of VAMP5 were categorized as type IIa fibers on the basis of their myosin heavy chain subtypes. In addition, the expression patterns of VAMP5 and glucose transporter 4 (GLUT4) were similar. In cardiac muscle, we determined that VAMP5 was localized to the vicinity of intercalated discs. These results suggest that VAMP5 plays local roles in membrane trafficking in skeletal and cardiac muscle.