The Multifunctional Effects of Nobiletin and Its Metabolites In Vivo

Nobiletin (NOB) chemically known as 5,6,7,8,3′,4′-hexamethoxyflavone is a dietary polymethoxylated flavonoid found in Citrus fruits. Recent evidences show that NOB is a multifunctional pharmaceutical agent. The various pharmacological activities of NOB include neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. These events may be underpinned by modulation of signaling cascades, including PKA/ERK/MEK/CREB, NF-κB, MAPK, Ca2+/CaMKII, PI3K/Akt1/2, HIF-1α, and TGFβ signaling pathways. The metabolites may exhibit stronger beneficial effects than NOB on diseases pathogenesis. The biological activities of NOB have been clarified on many systems. This review aims to discuss the pharmacological effects of NOB with specific mechanisms of actions. NOB may become a promising candidate for potential drug development. However, further investigations of NOB on specific intracellular targets and clinical trials are still needed, especially for in vivo medical applications

Acute myocardial infarction after inactivated COVID-19 vaccination: a case report and literature review

A number of vaccines have been developed and deployed globally to restrain the spreading of the coronavirus disease 2019 (COVID-19). The adverse effect following vaccination is an important consideration. Acute myocardial infarction (AMI) is a kind of rare adverse event after COVID-19 vaccination. Herein, we present a case of an 83-year-old male who suffered cold sweat ten minutes after the first inactivated COVID-19 vaccination and AMI one day later. The emergency coronary angiography showed coronary thrombosis and underlying stenosis in his coronary artery. Type II Kounis syndrome might be a potential mechanism, which is manifested as coronary thrombosis secondary to allergic reactions in patients with underlying asymptomatic coronary heart disease. We also summarize the reported AMI cases post COVID-19 vaccination, as well as overview and discuss the proposed mechanisms of AMI after COVID-19 vaccination, thus providing insights for clinicians to be aware of the possibility of AMI following COVID-19 vaccination and potential underlying mechanisms

Insights into the Action Mechanisms of Traditional Chinese Medicine in Osteoarthritis

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by articular cartilage destruction, synovial inflammation, and osteophyte formation. No effective treatments are available. The current pharmacological medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, accompanied by possible adverse effects, might ameliorate OA symptoms. But they do not arrest the progression of OA. Traditional Chinese medicine (TCM) provides medical value by modification of disease and symptoms in OA. Valuable work on exploring TCM merits for OA patients has been investigated using modern technologies, although the complicated interacting network among the numerous components indicates the uncertainty of target specification. This review will provide an overview of the action mechanism of TCM in the last 5 years, discussing the TCM activities of anti-inflammation, antiapoptosis, antioxidation, anticatabolism, and proliferation in OA. TCM is a proposed medical option for OA treatment

Extraction optimisation and isolation of triterpenoids from <i>Ganoderma lucidum</i> and their effect on human carcinoma cell growth

<div><p>The response surface methodology was used to optimise the extraction conditions of <i>Ganoderma lucidum</i> based on a Box–Behnken design. A quadratic model sufficiently simulated the response of ganoderic acid H with a determination coefficient (<i>R</i>²) of 0.98. The optimal condition for extracting triterpenoids was determined to be 100.00% ethanol at 60.22°C for 6.00 h, under which the yield of the reference triterpenoid ganoderic acid H increased from 0.88 to 2.09 mg/g powder. Following extraction, triterpenoid-enriched fraction was further isolated into 23 fractions, and 7 fractions were identified as ganoderic acids A, B, D, G, H and I and ganoderenic acid D. Of the seven triterpenoids, ganoderenic acid D was most cytotoxic with IC₅₀ values of 0.14 ± 0.01, 0.18 ± 0.02 and 0.26 ± 0.03 mg/mL in Hep G2, Hela and Caco-2 cells, respectively. While ganoderic acids A, G and H were relatively non-cytotoxic. The variation of inhibitory effects for these triterpenoids was likely related to their chemical structures.</p></div

Establishment of A Patient-derived Xenotransplantation Animal Model for Small Cell Lung Cancer and Drug Resistance Model

Background and objective Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. Methods Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm3 with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. Results Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient’s tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). Conclusion The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC

A fast response & recovery H2S gas sensor based on α-Fe2O3 nanoparticles with ppb level detection limit

H2S gas sensor based on α-Fe2O3 nanoparticles was fabricated by post-thermal annealing of Fe3O4 precursor which was synthesized using a facile hydrothermal route. The characteristic techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were adopted to characterize the chemical composition and microstructure of the obtained samples. Gas-sensing performance of the sensor was investigated at different operation temperatures from 100 °C to 400 °C. Results showed that the sensor exhibited the best sensitivity, reproducibility and long-term stability for detecting H2S gas at an operating temperature of 300 °C. The detection limit towards H2S gas was 0.05 ppm, and the response time and recovery time was 30 s and 5 s, respectively. In addition, sensing mechanism of the sensor towards H2S was discussed

7-Ketocholesterol Induces Oxiapoptophagy and Inhibits Osteogenic Differentiation in MC3T3-E1 Cells

7-Ketocholesterol (7KC) is one of the oxysterols produced by the auto-oxidation of cholesterol during the dysregulation of cholesterol metabolism which has been implicated in the pathological development of osteoporosis (OP). Oxiapoptophagy involving oxidative stress, autophagy, and apoptosis can be induced by 7KC. However, whether 7KC produces negative effects on MC3T3-E1 cells by stimulating oxiapoptophagy is still unclear. In the current study, 7KC was found to significantly decrease the cell viability of MC3T3-E1 cells in a concentration-dependent manner. In addition, 7KC decreased ALP staining and mineralization and down-regulated the protein expression of OPN and RUNX2, inhibiting osteogenic differentiation. 7KC significantly stimulated oxidation and induced autophagy and apoptosis in the cultured MC3T3-E1 cells. Pretreatment with the anti-oxidant acetylcysteine (NAC) could effectively decrease NOX4 and MDA production, enhance SOD activity, ameliorate the expression of autophagy-related factors, decrease apoptotic protein expression, and increase ALP, OPN, and RUNX2 expression, compromising 7KC-induced oxiapoptophagy and osteogenic differentiation inhibition in MC3T3-E1 cells. In summary, 7KC may induce oxiapoptophagy and inhibit osteogenic differentiation in the pathological development of OP

KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/STAT3 axis

Background: Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma characterized by high cellular proliferation and early metastatic spread. Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) can regulate tumor generation and development, including in SCLC. The current study aimed to assess the effect of the lncRNA, KCNQ1OT1, on the proliferation, apoptosis, and chemoresistance of SCLC and the potential underlying molecular mechanism. Methods: Matched chemo-resistant and sensitive cells were applied to RNA isolation and followed by expression profiling by microarray analysis and subsequent quantitative polymerase chain reaction (qPCR) validation. Cell viability and apoptosis were determined by Cell Counting Kit-8 and flow cytometry to examine the chemoresistance and apoptosis of KCNQ1OT1 knockdown with lentivirus-mediated RNA interference. Furthermore, cell proliferation was studied by colony formation, and invasion and migration were tested by Transwell cell invasion and wound-healing assays, respectively. A tumor xenograft model was established to determine the role of KCNQ1OT1 in tumor growth and chemoresistance in response to KCNQ1OT1 knockdown in vivo. Western blot analysis, qPCR, and immunohistochemistry were used to detect the levels of messenger RNA (mRNA) Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway-related markers. Results: Higher expression of KCNQ1OT1 was detected in SCLC chemo-resistant verso chemo-sensitive cells. Knockdown of KCNQ1OT1 inhibited SCLC cell viability and cloning ability, hindered cell migration and invasion, induced apoptosis in vitro, and suppressed tumor growth and chemoresistance in vivo, by activating the JAK2/STAT3 signaling pathway. Conclusions: This is the first study to indicate that lncRNA KCNQ1OT1 promotes cell proliferation and invasion, and prevents apoptosis of SCLC by activating the JAK2/STAT3 pathway

Additional file 2: Figure S2. of Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2

TUG1 promoted migration and invasion of SCLC cells in vitro. (A) Cell migration was quantified by wound healing assay. Cells were imaged immediately (0 h) and 24 h after scratches were created to measure the percentage of wound healed area. Representative images at different time points are shown. (B) Cell morphology graph of invasive cells in H446, H69AR and H446DDP cells after stable transfection of shTUG1 or shControl. Data represent mean ± SD of three independent experiments. (TIF 5658 kb