Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats.

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

Flexible nanohybrid substrates utilizing gold nanocubes/nano mica platelets with 3D lightning-rod effect for highly efficient bacterial biosensors based on surface-enhanced Raman scattering.

In this study, gold nanocubes (AuNCs) were quickly synthesized using the seed-mediated growth method and reduced onto the surface of two-dimensional (2D) delaminated nano mica platelets (NMPs), enabling the development of AuNCs/NMPs nanohybrids with a 3D lightning-rod effect. First, the growth-solution amount can be changed to easily adjust the AuNCs average-particle size within a range of 30-70 nm. The use of the cationic surfactant cetyltrimethylammonium chloride as a protective agent allowed the surface of AuNCs and nanohybrids to be positively charged. Positively charged nanohybrid surfaces presented a good adsorption effect for detecting molecules with negative charges on the surface. Additionally, the NMP surfaces were rich in ionic charges and provided a large specific surface area for stabilizing the growth of AuNCs. Delaminated AuNCs/NMPs nanohybrids can generate a 3D hotspot effect through self-assembly to enhance the Raman signal. Surface-enhanced Raman scattering (SERS) is highly sensitive in detecting adenine biomolecules. Its limit of detection (LOD) and Raman enhancement factor reached 10-9 M and 3.6 × 108, respectively. Excellent reproducibility was obtained owing to the relatively regular arrangement of AuNC particles, and the relative standard deviation (RSD) was 10.7%. Finally, the surface of NMPs was modified by adding the hydrophilic poly(oxyethylene)-diamine (POE2000) and amphiphilic PIB-POE-PIB copolymer at different weight ratios. The adjustment of the surface hydrophilicity and hydrophobicity of AuNCs/NMPs nanohybrids led to better adsorption and selectivity for bacteria. AuNCs/POE/NMPs and AuNCs/PIB-POE-PIB/NMPs were further applied to the SERS detection of hydrophilic Staphylococcus aureus and hydrophobic Escherichia coli, respectively. The SERS-detection results suggest that the LOD of hydrophilic Staphylococcus aureus and hydrophobic Escherichia coli reached 92 CFU mL-1 and 1.6 × 102 CFU mL-1, respectively. The AuNCs/POE/NMPs and AuNCs/PIB-POE-PIB/NMPs nanohybrids had different hydrophilic-hydrophobic affinities, which greatly improved the selectivity and sensitivity for detecting bacteria with different hydrophilicity and hydrophobicity. Therefore, fast, highly selective, and highly sensitive SERS biological-detection results were obtained.

Plumbagin Induces Reactive Oxygen Species and Endoplasmic Reticulum Stress-related Cell Apoptosis in Human Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC), a major malignancy in Taiwan, is an invasive epithelial neoplasm resulting in a low survival rate. Current treatments do not prevent OSCC progression, and antitumor therapies should be improved. Plumbagin, a natural compound extracted from Plumbago zeylanica L., appears to have antitumor effects in various tumors. The antitumor mechanism of plumbagin in OSCC is still unclear. This study investigated the molecular mechanism through which plumbagin induces apoptosis. MATERIALS AND METHODS: To investigate the antiproliferative and pro-apoptotic effects of Plumbagin on OSCC cells and explore its underlying mechanism, cell counting kit-8, cell cycle analysis, and annexin V/PI assay were conducted. The functions of plumbagin on endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) deficiency were analyzed using flow cytometric analysis. Plumbagin-induced apoptosis-associated proteins were detected using western blotting. RESULTS: Plumbagin induced apoptosis in OSCC cells by suppressing tumor cell proliferation through ROS production, ER stress, mitochondrial dysfunction, and caspases activation. CONCLUSION: Plumbagin is a promising antitumor candidate targeting human OSCC.

Pregnancy maintenance and fetal loss assessment in Holstein cows through analyzing pregnancy-associated glycoproteins in milk.

Fetal loss (FL) from the 45th day of gestation until calving can impose a significant economic burden on dairy farmers, resulting in lost profits and increased production costs. Pregnancy-associated glycoprotein (PAG) is commonly used for detecting pregnancy in cows. PAG is secreted by binucleated trophoblast cells of the placenta and regulated by more than 24 genes. The purpose of this study was to determine the PAG threshold for FL and a probability of pregnancy maintenance until calving based on milk PAG levels. Our results reveal that primiparous and multiparous cows that maintained pregnancy until the 40th week exhibited higher PAG sample-negative (SN) values in their milk in the 6th week of gestation than did those that experienced FL later in gestation. Pregnant cows with higher PAG SN values in the 6th week of gestation were more likely to maintain their pregnancies. The area under the receiver operating characteristic curve for predicting the probability of pregnancy maintenance was 0.722 for our prediction model. On the other hand, a milk PAG SN value of <0.192 indicated 95 % confidence that FL would occur between the 7th and 40th weeks of gestation. Milk PAG testing is a noninvasive sampling technique that does not induce additional stress in lactating cows. The study reveals that PAG SN values increase significantly in Holstein cows during the 6th week of gestation. The predictive model developed was effective in forecasting pregnancy outcomes up to the 40th week of gestation or calving. The model's performance is moderately good for field application and could be a useful tool for dairy producers.

Chronopharmacology of diuresis via metabolic profiling and key biomarker discovery of the traditional Chinese prescription Ji-Ming-San using tandem mass spectrometry in rat models.

BACKGROUND: Ji-Ming-Shan (JMS) is a traditional prescription used for patients with rheumatism, tendons swelling, relief of foot pain, athlete's foot, diuresis, gout. Although many studies have investigated the active compounds in each herb, the functional mechanism behind its therapeutic effect remains unclear. STUDY DESIGN: Metabolic cages for sample collection. The serum components obtained from the experimental animals were analyzed using LC-MS/MS. Furthermore, cross-analysis using the software MetaboAnalyst and Venn diagrams were used to investigate chronopharmacology of JMS in the animal models. PURPOSE: The aim of this study is to analyze the diuretic effects of JMS and to explore their chronopharmacology involved in organ regulation through four-quarter periods from serum samples of rat models. METHODS: Metabolic cages were used for collecting the urine samples and PocketChem UA PU-4010, Fuji DRI-CHEM 800 were used to examine the urine biochemical parameters. The serum components were identified through ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-Q-TOF) with a new developed method. Cross analysis, Venn diagram, MetaboAnalyst were used to investigate the key biomarker and major metabolism route with the oral administration of the drug. RESULT: JMS significantly changed the 6 h urine volume with no observed kidney toxicity. Urine pH value ranges from 7.0 to 7.5. The chronopharmacology of JMS diuresis activity were 0-6 and 6-12 groups. UPLC-Q-TOF analyses identified 243 metabolites which were determined in positive mode and negative mode respectively. With cross analysis in the Venn diagram, one key biomarker naringenin-7-O-glucoside has been identified. Major metabolic pathways such as 1: Glycerophospholipid metabolism, 2: Primary bile acid biosynthesis, 3: Sphingolipid metabolism, 4: Riboflavin metabolism, 5: Linoleic acid metabolism, 6: Butanoate metabolism. CONCLUSION: JMS significantly changed the urine output of animals in the 0-6 and 6-12 groups. No change in urine pH was observed and also kidney toxicity. A new UPLC-Q-TOF method was developed for the detection of the metabolites of JMS after oral administration. The cross analysis with Venn diagram and identified the key biomarker of JMS namely naringenin-7-O-glucoside. The results showed that six major pathways are involved in the gastrointestinal system and the liver. This study demonstrated the capability of JMS prescription in the regulation of diuresis and identified a key biomarker that is responsible for its therapeutic effect.

Anti-COVID-19, Anti-Inflammatory, and Anti-Osteoarthritis Activities of Sesamin from Sesamum indicum L.

During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as "long COVID" and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin's anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin's anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25-50 µM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25-50 µM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin's binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development.

CX3CL1 induces cell migration and invasion through ICAM-1 expression in oral squamous cell carcinoma cells.

Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C-X3-C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1-induced cell motility is upregulated through intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre-treated with CX3CR1 monoclonal antibody (mAb) and small-interfering RNA (siRNA). The CX3CL1-CX3CR1 axis activates promoted PLCß/PKCα/c-Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein-1 (AP-1) activity. The CX3CR1 mAb and PLCß, PKCα, c-Src inhibitors reduced CX3CL1-induced c-Jun phosphorylation, c-Jun translocation into the nucleus and c-Jun binding to the ICAM-1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM-1 expression through the CX3CR1 and the PLCß/PKCα/c-Src signal pathway, suggesting that CX3CL1-CX3CR1-mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.

Chemopreventive effects of Xiang Sha Liu Jun Zi Tang on paclitaxel-induced leucopenia and neuropathy in animals.

Paclitaxel frequently induces peripheral neuropathy and myelosuppression during cancer treatment. According to the National Health Insurance Research Database of Taiwan, traditional Chinese medicine doctors widely use Xiang Sha Liu Jun Zi Tang (XSLJZT) to treat breast cancer patients who have received paclitaxel. We explored the combined therapeutic effects of XSLZJT with paclitaxel. XSLJZT did not exhibit significant cytotoxic effects on P388-D1 cells; however, the combination of XSLJZT (100 and 500 mg/kg) with paclitaxel prolonged the survival rate in P388-D1 tumor-bearing mice compared to paclitaxel-only. In addition, XSLJZT was found to enhance white blood cells (WBC) counts and promote leukocyte rebound in paclitaxel-induced leukopenia in mice. XSLJZT also reduced paclitaxel-induced mechanical pain and inhibited c-Fos protein expression in the L4-6 spinal cords of Wistar rats. Moreover, paclitaxel-induced shortening of the nerve fibers of dorsal root ganglion cells was ameliorated by pre-treatment with XSLJZT. Therefore, we suggest that XSLJZT could be used as an adjunct for cancer patients, as the formula could decrease paclitaxel-induced neuropathy and myelosuppression.

The First Nationwide Surveillance of Severe Fever with Thrombocytopenia Syndrome in Ruminants and Wildlife in Taiwan.

Since the first discovery of severe fever with thrombocytopenia syndrome virus (SFTSV) in China in 2009, SFTSV has rapidly spread through other Asian countries, including Japan, Korea, Vietnam and Pakistan, in chronological order. Taiwan reported its first discovery of SFTSV in sheep and humans in 2020. However, the prevalence of SFTSV in domestic and wildlife animals and the geographic distribution of the virus within the island remain unknown. A total of 1324 animal samples, including 803 domestic ruminants, 521 wildlife animals and 47 tick pools, were collected from March 2021 to December 2022 from 12 counties and one terrestrial island. The viral RNA was detected by a one-step real-time reverse transcription polymerase chain reaction (RT-PCR). Overall, 29.9% (240/803) of ruminants showed positive SFTSV RNA. Sheep had the highest viral RNA prevalence of 60% (30/50), followed by beef cattle at 28.4% (44/155), goats at 28.3% (47/166), and dairy cows at 27.5% (119/432). The bovine as a total of dairy cow and beef cattle was 27.8% (163/587). The viral RNA prevalence in ticks (predominantly Rhipicephalus microplus) was similar to those of ruminants at 27.7% (13/47), but wild animals exhibited a much lower prevalence at 1.3% (7/521). Geographically the distribution of positivity was quite even, being 33%, 29.1%, 27.5% and 37.5% for northern, central, southern and eastern Taiwan, respectively. Statistically, the positive rate of beef cattle in the central region (55.6%) and dairy cattle in the eastern region (40.6%) were significantly higher than the other regions; and the prevalence in Autumn (September-November) was significantly higher than in the other seasons (p < 0.001). The nationwide study herein revealed for the first time the wide distribution and high prevalence of SFTSV in both domestic animals and ticks in Taiwan. Considering the high mortality rate in humans, surveillance of other animal species, particularly those in close contact with humans, and instigation of protective measures for farmers, veterinarians, and especially older populations visiting or living near farms or rural areas should be prioritized.

Cinnamic aldehyde, an anti-inflammatory component in Du-Huo-Ji-Sheng-Tang, ameliorates arthritis in II collagenase and monosodium iodoacetate induced osteoarthritis rat models.

Background and aim: Du-Huo-Ji-Sheng-Tang (DHJST) is a Chinese herbal formula used for arthralgia and arthritis treatment clinically. This study aims to evaluate the joint-protecting efficacy of DHJST and to identify the active constituents as the evaluation marker. Experimental procedure: DHJST can be categorized into three recipes: Blood-tonifying-herbs Si-Wu-Tang (SWT), Wind-dampness-dispelling-herbs (WDH) and Qi-tonifying-herbs (TH). All formulas were used to explore the joint-protecting efficacies. Results and conclusion: s: Firstly, DHJST could decrease the arthritis progression in the monosodium-iodoacetate-induced rat and cure arthritis in the type II collagenase-induced rat. Further, in lipopolysaccharide-stimulated RAW 264.7 cells, DHJST, TH and Cinnamomum cassia (CC), an ingredient in TH, were the most potent nitric oxide (NO) and prostaglandin E2 (PGE2) inhibitors. The major components, cinnamic aldehyde, showed the strongest NO and PGE2 inhibition. Up-regulated inducible NO synthase (iNOS) and cyclooxygenase-2 were inhibited by DHJST, TH, CC, and cinnamic aldehyde. In interleukin-1ß-stimulated primary chondrocytes, upregulated iNOS was inhibited by DHJST, TH, Cinnamomum cassia, and cinnamic aldehyde. Upregulated matrix metalloprotease-13 was only inhibited by DHJST and TH and Eucommia ulmoides (EU) extract. Results suggest that DHJST presented joint-protective and cure arthritis effects. TH presented equal joint-protective effects as DHJST. The major anti-inflammatory ingredient in TH was Cinnamomum cassia in TH. And cinnamic aldehyde was the potent anti-inflammatory active compound in Cinnamomum cassia. Therefore, this study may facilitate the modern use of DHJST with TH as a simplified version but equally effective anti-osteoarthritic agents with cinnamic aldehyde as a quality control marker of DHJST and TH in osteoarthritis prevention or treatment.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

In vitro and in vivo anti-osteoarthritis effects of tradition Chinese prescription Ji-Ming-San.

ETHNOPHARMACOLOGICAL RELEVANCE: Ji-Ming-Shan (JMS) is a traditional herbal prescription consisting of seven herbs including Areca cathechu Burm.f., Citrus reticulata Blanco, Chaenomeles speciosa (Sweet) Nakai, Euodia ruticarpa (A. Juss.) Benth., Perilla frutescens (L.) Britton, Zingiber officinale Roscoe, Platycodon grandiflorus (Jacq.). It was first recorded during the Song dynasty and has been used extensively for protection against rheumatism, treatment of swelling of tendons, relief from foot pain, gout and diuresis and other forms of inflammation. AIM OF THE STUDY: The aim of this study is to evaluate the anti-inflammatory and anti-osteoarthritis activity of JMS extracts with the use of different cell lines (RAW 264.7 cells, SW1353 cells and primary cultured rat chondrocytes). MIA-induced rat animal models were used to assess the anti-osteoarthritis activity of the extract. MATERIALS AND METHODS: This study investigated the anti-inflammatory activity of JMS-95E on LPS-induced RAW 264.7 macrophages and IL-1ß-stimulated chondrocytes. For the in vivo study, male Wistar rats were used and they were randomly assigned in different groups: blank, control, positive control and three different JMS-95E treatment groups (200, 400, 800 mg/kg/d). Paw edema, hind-limb weight bearing, serum inflammatory cytokines including hematoxylin and eosin (HE) staining experiments were used to assess the efficacy of the extract in the rat model. RESULT: JMS 95% ethanol extract (JMS-95E, marker substance: narirutin (5.10 mg/g) and hesperidin (11.33 mg/g) has been identified in the extract using high pressure liquid chromatography. For in vitro assays, JMS-95E did not exhibit cytotoxicity and was able to downregulate the protein expression of iNOS, COX-2 and MMP-13. The production of inflammatory mediators such as NO and PGE2 were also reduced with an increase in dose-dependent manner in various cell lines. Inhibitory activity on the key enzyme xanthine oxidase was also observed in this study. In rat animal models, JMS-95E reduced the inflammatory responses such as acute swelling, chondrocyte degradation and pain section of paw edema in rat model. Molecular marker studies of inflammation demonstrated that JMS-95E significantly decrease PGE2 expression in MIA model. CONCLUSION: JMS-95E inhibited the inflammatory pathway leading to the production or expression levels of NO, iNOS, COX-2 and PGE2 in macrophage cells. In primary cultured rat chondrocytes iNOS and SW1353 MMP-13 expression were downregulated after JMS-95E treatment. For the in vivo study JMS-95E significantly reduced the paw volume of carrageenan-induced rat paw edema through each dose and significantly inhibited paw volume, counterweight the distribution of hind-paw weight bearing through the MIA model which means JMS-95E could promote recovery of the acute swelling and chondrocyte degradation of the ankle joints. The above results provided the multiple mechanism of JMS-95E in OA treatment of the scientific founding which supported the description of JMS in traditional use.

Hepatoprotective effect of botanical drug formula on high-fat diet-induced non-alcoholic fatty liver disease by inhibiting lipogenesis and promoting anti-oxidation.

With the prevalence of obesity and other components of metabolic syndrome, Non-alcoholic fatty liver disease (NAFLD) has become increasingly common. In recent years, much attention has been paid to various plant sources, hoping to find a treatment for NAFLD in plants. The Livsooth authentic herbal formula (LAH, ), a botanical drug formula combined with Puerariae lobatae radix, Lonicerae japonicae flos, Hoveniae semen, and Siraitiae fructus. This study used a network pharmacology approach to predict the potential mechanisms of LAH against NAFLD. Gene Ontology (GO) and KEGG pathway enrichment analyses have identified potential biochemical and signaling pathways. Subsequently, the potential mechanism of action of LAH on NAFLD predicted by network pharmacology analysis was validated in a high-fat diet (HFD)-induced NAFLD model in C57BL/6 mice. Our results demonstrated that LAH ameliorated hepatocyte steatosis in liver tissue by activating the AMPK pathway and decreasing serum triglycerides, low-density lipoprotein, glucose, and cholesterol. Besides, LAH increased the hepatic antioxidant enzymes activities, suggested that LAH improved oxidative stress markers in HFD induced NAFLD mice. In vitro experiments confirmed that the active component of LAH, puerarin, regulates lipid accumulation through the AMPK pathway. In conclusion, our study shows that network pharmacology predictions are consistent with experimental validation. LAH can be a candidate supplement for the prevention of NAFLD.

Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes.

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk scores are constructed and validated for absolute risks prediction of T2D in Taiwanese population. In conclusion, our data-driven approach without a priori hypothesis is useful for novel gene discovery and validation on top of disease risk prediction for unique non-European population.

Triangular gold nanoplates/two-dimensional nano mica platelets with a 3D lightning-rod effect as flexible nanohybrid substrates for SERS bacterial detection.

Triangular gold nanoplates (TAuNPs) were prepared by a one-step rapid growth method and then reduced and stabilized on two-dimensional nano mica nanoplatelets (NMPs). We also prepared TAuNP/NMP nanohybrids with a three-dimensional lightning-rod effect by oxidative etching. The surface of the delaminated NMPs (only 1 nm thick) is highly charged and can provide a large specific surface area; thus, it can be used as a substrate for the stable growth of gold nanoplates. In addition, by controlling relevant synthesis parameters, the edge length of the TAuNPs can be easily adjusted in the range of 30-90 nm. During reduction of the TAuNPs, the cationic surfactant cetyltrimethylammonium chloride was added as a protective agent to surround the TAuNPs; consequently, the surface was positively charged, which facilitates adsorption for detecting molecules with negative charges. When nanohybrids were used in surface-enhanced Raman spectroscopy (SERS) to detect adenine molecules, the limit of detection concentration was 10-9 M. The Raman enhancement factor was 5.7 × 107, and the relative standard deviation (RSD) was 9.8%. Finally, this method was applied to the biological detection of Staphylococcus aureus, and the surface charge and hydrophilic properties of the material significantly improved the SERS signal of S. aureus. The limit of detection concentration was 102 CFU mL-1, and the RSD was 11.2%. The TAuNP/NMP nanohybrids can provide very rapid and sensitive SERS detection of biomolecules.

De Novo Mosaic 6p23-p25.3 Tetrasomy Caused by a Small Supernumerary Marker Chromosome Presenting Trisomy Distal 6p Phenotype: A Case Report and Literature Review.

Small supernumerary marker chromosomes (sSMCs) derived from the chromosome 6 short arm are rare and their clinical significance remains unknown. No case with sSMC(6) without centromeric DNA has been reported. Partial trisomy and tetrasomy of distal 6p is a rare but clinically distinct syndrome. We report on a de novo mosaic sSMC causing partial tetrasomy for 6p23-p25.3 in a male infant with symptoms of being small for gestational age, microcephaly, facial dysmorphism, congenital eye defects, and multi-system malformation. Conventional cytogenetic analysis revealed a karyotype of 47,XY,+mar [25]/46,XY [22]. Array comparative genomic hybridization (aCGH) revealed mosaic tetrasomy of distal 6p. This is the first case of mosaic tetrasomy 6p23-p25.3 caused by an inverted duplicated neocentric sSMC with characteristic features of trisomy distal 6p. Comparison of phenotypes in cases with trisomy and tetrasomy of 6p23-p25.3 could facilitate a genotype-phenotype correlation and identification of candidate genes contributing to their presentation. The presentation of anterior segment dysgenesis and anomaly of the renal system suggest triplosensitivity of the FOXC1 gene. In patients with microcephaly growth retardation, and malformation of the cardiac and renal systems, presentation of anterior segment dysgenesis might be indicative of chromosome 6p duplication, and aCGH evaluation should be performed for associated syndromic disease.

KI Essence extract (a spleen-tonifying formula) promotes neurite outgrowth, alleviates oxidative stress and hypomyelination, and modulates microbiome in maternal immune activation offspring.

Mushrooms and Chinese traditional herbs have bioactive nutraceuticals with multiple therapeutic functions, including antioxidant and antibacterial activities and microbiome modulation properties. Mushroom-derived bioactive compounds are used in medicines for the treatment of neurological disorders with abnormal brain-gut-microbiome axis. This study examined the effects of KI Essence extract, a spleen-tonifying formula, on neurite growth, antioxidant activity, hypomyelination modulation, and the microbiome profile in lipopolysaccharide (LPS)-induced maternal immune activation (MIA) offspring. The KI Essence extract induced PC12 cell neurite growth by increasing extracellular signal-regulated kinase (ERK) phosphorylation, promoting 2,2'-diphenyl-1-picrylhydrazyl radical scavenging activity, reducing the level of tert-butylhydroperoxide-induced lipid peroxidation in brain homogenates, protecting PC12 cells from H2O2-induced cell death (through the inhibition of ERK phosphorylation), alleviating hypomyelination, and downregulating interleukin-1ß through LPS-activated microglia production; moreover, the numbers of Enterobacteriaceae, Actinobacteria, Peptostreptococcaceae, Erysipelotrichaceae, and Bifidobacterium bacteria in MIA offspring increased. In summary, the KI Essence extract promotes neurite outgrowth, alleviates oxidative stress and hypomyelination, and modulates microbiota dysbiosis in MIA offspring.

Synergistic deciphering of bioenergy production and electron transport characteristics to screen traditional Chinese medicine (TCM) for COVID-19 drug development.

Background: Traditional Chinese medicine (TCM) has been used as an "immune booster" for disease prevention and clinical treatment since ancient China. However, many studies were focused on the organic herbal extract rather than aqueous herbal extract (AHE; decoction). Due to the COVID-19 pandemics, this study tended to decipher phytochemical contents in the decoction of herbs and derived bioactivities (e.g., anti-oxidant and anti-inflammatory properties). As prior works revealed, the efficacy of Parkinson's medicines and antiviral flavonoid herbs was strongly governed by their bioenergy-stimulating proficiency. Methods: Herbal extracts were prepared by using a traditional Chinese decoction pot. After filtration and evaporation, crude extracts were used to prepare sample solutions for various bioassays. The phytochemical content and bioactivities of AHEs were determined via ELISA microplate reader. Microbial fuel cells (MFCs) were used as a novel platform to evaluate bioenergy contents with electron-transfer characteristics for antiviral drug development. Significant findings: Regarding 18 TCM herbal extracts for the prevention of SARS and H1N1 influenza, comparison on total polyphenol, flavonoid, condensed tannins and polysaccharides were conducted. Moreover, considerable total flavonoid contents were detected for 11 herb extracts. These AEHs were not only rich in phytonutrient contents but also plentiful in anti-oxidant and anti-inflammatory activities. Herbs with high polyphenol content had higher antioxidant activity. Forsythia suspensa extract expressed the highest inhibition against nitric oxide production for anti-inflammation. MFC bioenergy-stimulating studies also revealed that top ranking COVID-19 efficacious herbs were both bioenergy driven and electron mediated. That is, electron transfer-controlled bioenergy extraction was significant to antiviral characteristics for anti-COVID-19 drug development.

Gender differences in the association between oral health literacy and oral health-related quality of life in older adults.

BACKGROUND: Poor oral health affects quality of life; oral health literacy studies are increasing as it plays an essential role in promoting oral health. However, little is known regarding the gender differences in oral health literacy and oral health-related quality of life (OHRQoL) among older adults. This study aimed to explore the gender differences in oral health literacy and OHRQoL among community-dwelling older adults in Taiwan. METHODS: A cross-sectional study design with convenience sampling was undertaken to recruit participants at two community service centres. Data were collected using a structured survey consisted of the demographic characteristics, instrumental activities of daily living, nutrition assessment, oral health literacy and OHRQoL. The logistic regression was used to examine the gender differences in the relationship between oral health literacy and OHRQoL. RESULTS: A total of 202 participants completed the survey. Of which 56.4% (n = 114) were female. Logistic regression analyses showed that after controlling for age, instrumental activities of daily living, nutrition, education level, and average monthly income, better oral health literacy was associated with better oral health quality of life (p = 0.006) in men. CONCLUSIONS: The relationship between oral health literacy and OHRQoL was only significant for men. No significant relationship between women's oral health literacy and their OHRQoL. However, good OHRQoL is an integral part of overall health, but it is affected by differences in oral health and the accessibility of healthcare services. We suggest that gender-specific oral health literacy education should be offered through community health-education programs.

Naringenin induces endoplasmic reticulum stress-mediated cell apoptosis and autophagy in human oral squamous cell carcinoma cells.

Human oral squamous cell carcinoma (OSCC) has been one of the most common oral cancers owing to high percentage of betel nuts chewers, smokers, and alcohol consumption. With current treatment strategies in OSCC, more than half patients relapse and develop distant metastases with poor prognosis. To overcome the incident, OSCC poses a challenge in current therapies and treatments. Naringenin, a natural flavonoid, has been noted for antitumor effects on various types of cancers; however, the effects of naringenin on OSCC remain bias. In this study, naringenin demonstrated the potential multifunction in human OSCC cells not only leading to cell apoptosis, but also alternating the general function of autophagy, serving as pro-survival mechanism by inducing the endoplasmic reticulum (ER) stress signaling through intracellular reactive oxygen species (ROS) production. In the process of programmed cell death, naringenin induced apoptotic signaling through caspase-cascade, mitochondrial dysfunction, and ER stress by aberrance of Ca2+ release. In contrast, under the presence of naringenin, the pro-survival has been altered into pro-death to activate the caspases-mediated apoptosis achieving cell death. The cross-function of apoptosis and autophagy has demonstrated the effect of naringenin-induced intracellular ROS activity in OSCC cells. Therefore, this study found that the effect of naringenin induces intracellular ROS to trigger programmed cell death and ER stress through the mechanisms of apoptosis and autophagy in human oral squamous carcinoma. PRACTICAL APPLICATIONS: This study revealed that naringenin debilitated the OSCC cell viability via the intracellular ROS production, ER stress, and autophagy, leading to cell apoptosis. Based on these studies and findings, naringenin provided an antitumor effect as a novel natural compound to improve the current therapies in OSCC.