Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Solanum nigrum L. berries extract ameliorated the alcoholic liver injury by regulating gut microbiota, lipid metabolism, inflammation, and oxidative stress.

Solanum nigrum L. (SN) berry is an edible berry containing abundant polyphenols and bioactive compounds, which possess antioxidant and antiinflammatory properties. However, the effects of SN on alcohol-induced biochemical changes in the enterohepatic axis remain unclear. In the current study, a chronic ethanol-fed mice ALD model was used to test the protective mechanisms of SN berries. Microbiota composition was determined via 16S rRNA sequencing, we found that SN berries extract (SNE) improved intestinal imbalance by reducing the Firmicutes to Bacteroides ratio, restoring the abundance of Akkermansia microbiota, and reducing the abundance of Allobaculum and Shigella. SNE restored the intestinal short-chain fatty acids content. In addition, liver transcriptome data analysis revealed that SNE primarily affected the genes involved in lipid metabolism and inflammatory responses. Furthermore, SNE ameliorated hepatic steatosis in alcohol-fed mice by activating AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPAR-α). SNE reduced the expression of toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88) nuclear factor kappa-B (NF-κB), which can indicate that SNE mainly adjusted LPS/TLR4/MyD88/NF-κB pathway to reduce liver inflammation. SNE enhanced hepatic antioxidant capacity by regulating NRF2-related protein expression. SNE alleviates alcoholic liver injury by regulating of gut microbiota, lipid metabolism, inflammation, and oxidative stress. This study may provide a reference for the development and utilization of SN resources.

Real-world data of China: Analysis of HPV vaccine coverage and post-vaccination adverse reaction monitoring in Western Chinese provinces from 2018 to 2021.

To investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine's safety profile.

Immediate and long-term changes in infectious diseases in China at the "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" stages from 2020 to 2022: a multistage interrupted-time-series-analysis.

BACKGROUND: From January 2020 to December 2022, China implemented "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" to block the COVID-19 epidemic; however, the immediate and long-term impact of three strategies on other infectious diseases and the difference in their impact is currently unknown. We aim to provide a more comprehensive understanding of the impact of non-pharmacological interventions (NPIs) on infectious diseases in China. METHODS: We collected data on the monthly case count of infectious diseases in China from January 2015 to July 2022. After considering long-term trends using the Cox-Stuart test, we performed the two ratio Z tests to preliminary analyze the impact of three strategies on infectious diseases. Next, we used a multistage interrupted-time-series analysis fitted by the Poisson regression to evaluate and compare the immediate and long-term impact of three strategies on infectious diseases in China. RESULTS: Compared to before COVID-19, the incidence of almost all infectious diseases decreased immediately at stages 1, 2, and 3; meanwhile, the slope in the incidence of many infectious diseases also decreased at the three stages. However, the slope in the incidence of all sexually transmitted diseases increased at stage 1, the slope in the incidence of all gastrointestinal infectious diseases increased at stage 2, and the slope in the incidence of some diseases such as pertussis, influenza, and brucellosis increased at stage 3. The immediate and long-term limiting effects of "Normalized-control" on respiratory-transmitted diseases were weaker than "First-level-response" and the long-term limiting effects of "Dynamic-COVID-zero" on pertussis, influenza, and hydatid disease were weaker than "Normalized-control". CONCLUSIONS: Three COVID-19 control strategies in China have immediate and long-term limiting effects on many infectious diseases, but there are differences in their limiting effects. Evidence from this study shows that pertussis, influenza, brucellosis, and hydatid disease began to recover at stage 3, and relaxation of NPIs may lead to the resurgence of respiratory-transmitted diseases and vector-borne diseases.

Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study.

BACKGROUND: The impact of COVID-19 on the epidemiology, clinical characteristics, and infection spectrum of viral and bacterial respiratory infections in Western China is unknown. METHODS: We conducted an interrupted time series analysis based on surveillance of acute respiratory infections (ARI) in Western China to supplement the available data. RESULTS: The positive rates of influenza virus, Streptococcus pneumoniae, and viral and bacterial coinfections decreased, but parainfluenza virus, respiratory syncytial virus, human adenovirus, human rhinovirus, human bocavirus, non-typeable Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae infections increased after the onset of the COVID-19 epidemic. The positive rate for viral infection in outpatients and children aged <5 years increased, but the positive rates of bacterial infection and viral and bacterial coinfections decreased, and the proportion patients with clinical symptoms of ARI decreased after the onset of the COVID-19 epidemic. Non-pharmacological interventions reduced the positive rates of viral and bacterial infections in the short term but did not have a long-term limiting effect. Moreover, the proportion of ARI patients with severe clinical symptoms (dyspnea and pleural effusion) increased in the short term after COVID-19, but in the long-term, it decreased. CONCLUSIONS: The epidemiology, clinical characteristics, and infection spectrum of viral and bacterial infections in Western China have changed, and children will be a high-risk group for ARI after the COVID-19 epidemic. In addition, the reluctance of ARI patients with mild clinical symptoms to seek medical care after COVID-19 should be considered. In the post-COVID-19 era, we need to strengthen the surveillance of respiratory pathogens.

In Vivo Metabolites of Panaxadiol Inhibit HepG-2 Cell Proliferation by Inducing G1 Arrest and ROS-Mediated Apoptosis.

In this study, 10 metabolites were obtained by collecting and extracting fecal samples after oral administration of panaxadiol (PD). Of these 10 metabolites, M7 (3ß,21ß,22α-hydroxy-24-norolean-12-ene), M8 (21ß,22α-hydroxy-24-norolean-12-ene-3-one), M9 (3ß,30α-hydroxy-24-norolean-22,30-epoxy-12-ene), and M10 (3ß,21ß-hydroxy-24-norolean-12-ene) were new compounds. MTT screening of the isolated compounds revealed that the inhibitions of cancer cells by M2, M4, M7, M8, and M10 were significantly stronger than that by the mother drug M0, with the activity of M2 being the most significant. Further, we investigated the anticancer mechanism of M2. The results showed that M2 significantly increased the level of ROS in cells; regulated the expressions of Bax, Bcl-2, and Cyt-C through the mitochondrial pathway; triggered the caspase cascade; and induced apoptosis. M2 could also induce G1 phase arrest and significantly regulate cell cycle-related proteins. In conclusion, the experimental results provide data for further study on the metabolic mechanism of PD in vivo and the potential of developing new anti-cancer drugs.

Accuracy of hepatitis B disease surveillance, Gannan prefecture, Gansu province, China; 2017.

Hepatitis B is a major global public health threat. According to China's National Notifiable Disease Reporting System (NNDRS), Gannan Tibetan Autonomous Prefecture (Gannan) had the highest incidence of hepatitis B in Gansu Province during 2004 to 2016. We evaluated NNDRS hepatitis B case reports from Gannan to determine accuracy of diagnosis and to understand factors associated with inaccuracy. We reviewed medical records with hepatitis B diagnosis hospitalized in seven county hospitals in Gannan between January 1, 2016 and July 31, 2017. Using national "Classification and Diagnostic Procedures for Hepatitis B," we independently reclassified the diagnoses. We determined the positive predictive value (PPV) of reported hepatitis B cases. We investigate clinicians' understanding of the diagnostic and reporting criteria for hepatitis B by questionnaire. We reviewed and re-categorized 400 inpatients reported. Sixteen cases had been reported as acute hepatitis B, but on re-categorization, none were acute hepatitis B cases. PPVs for chronic hepatitis B and unclassified hepatitis B cases were 66% and 15% respectively; 327 (82%) of the reported hepatitis B cases were inaccurately classified; 261 were carriers, 59 were reported previously, and 7 did not have hepatitis B. The actual incidence of hepatitis B in Gannan in 2016 was estimated to be 19/100,000, significantly below the reported incidence of 106/100,000. Among reported cases, 81% had been tested for Alanine aminotransferase, 52% for hepatitis C antibody, 80% with liver ultrasound, 32% for hepatitis A antibody, and 7% for hepatitis B virus (HBV) DNA. Not all cases were tested for anti-HBc IgM or hepatitis E antibody or had a liver biopsy. In the knowledge test, 56% of clinicians accurately diagnosed three simulated cases of acute hepatitis B, and 17% correctly diagnosed two simulated cases chronic hepatitis B; 22% knew that "a client with only HBsAg positivity need not be reported." The falsely high incidence in Gannan was due to diagnostic and reporting inaccuracies. We recommend that clinicians and laboratorians receive additional training in hepatitis B diagnostic criteria and reporting standards, including appropriate use of IgM anti-HBc tests. Hepatitis B surveillance data should be periodically reviewed and evaluated for accuracy.

Gypensapogenin H suppresses tumor growth and cell migration in triple-negative breast cancer by regulating PI3K/AKT/NF-κB/MMP-9 signaling pathway.

Due to its aggressiveness and high metastasis rates, triple-negative breast cancer (TNBC) is a ubiquitous and deadly disease for the majority of women globally. Gypensapogenin H (GH) is a novel dammarane-type triterpene isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. Our previous work demonstrated that GH promoted apoptosis in TNBC. In the present study, xenograft TNBC models (xenotransplantation of MDA-MB-231 cells in nude mice) were used to evaluate the efficacy of GH in vivo. We preliminarily predicted the mechanism of GH inhibiting breast cancer tumors at the gene level through transcriptome screening. Through western blot analysis of tumor tissue, we found that GH could inhibit tumor proliferation and migration by regulating the PI3K/AKT/NF-κB/MMP-9 signaling pathway in vivo. We also analyzedthe results at the cell level in vitro, which were consistent with those in vivo. In summary, GH inhibited TNBC growth in vivo and suppressed TNBC cell migration in vitro. Our findings could help understand the mechanism of action of GH and suggest that GH would be a promising agent for TNBC therapy.

Gypensapogenin I Suppresses Cell Proliferation in Triple-Negative Breast Cancer Via Triggering the Closure of AKT/GSK3ß/ß-Catenin and Notch-1 Signaling Pathways.

Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a natural damarane-type saponin, was obtained from the hydrolysates of total gypenosides. The present research was performed to investigate the potential antiproliferation effect of Gyp I in MDA-MB-231 cells and the underlying mechanisms. Here, we found that Gyp I attenuated survival, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells. Target prediction by binding molecule docking and western blot assays confirmed the mechanism by which Gyp I inhibited the proliferation of breast cancer cells via the AKT/GSK3ß/ß-catenin signaling pathway. We also showed that Gyp I exhibited superior in vivo efficacy that was dose dependent. Tumor tissue transcriptome analysis indicated that Gyp I could decrease the expression levels of NOTCH1 and HES1, which was in contrast to the effect on MAML and NUMBL, indicating that our compound hindered the activation of the Notch-1 signaling pathway. In summary, we report for the first time that Gyp I shows excellent anti-breast cancer activity in vivo and in vitro and that its pathway of action is related to the AKT/GSK3ß/ß-catenin and Notch-1 signaling pathways. Therefore, Jiaogulan tea can not only be used as a health food but also possesses the possibility to treat triple-negative breast cancer (TNBC).

Near-infrared light triggered multi-hit therapeutic nanosystem for tumor specific photothermal effect amplified signal pathway regulation and ferroptosis.

The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability. In recent years, scientists have devoted themselves to find a variety of treatments to solve this problem. Herein, we propose a multi-hit strategy that is based on the biodegradable hollow mesoporous Prussian blue (HMPB)-based nanosystem for tumor-specific therapy that encapsulated the critical heat shock protein 90 (HSP90) inhibitor 17-dimethylamino-ethylamino-17-demethoxydeldanamycin (17-DMAG). The nanosystem was further modified using thermotropic phase transition material star-PEG-PCL (sPP) and hyaluronic acid (HA), which offers near infrared light (NIR) responsive release characteristic, as well as enhanced tumor cell endocytosis. Upon cell internalization of 17-DMAG-HMPB@sPP@HA and under 808 nm laser irradiation, photothermal-conversion effect of HMPB directly kills cells using hyperthermia, which further causes phase transition of sPP to trigger release of 17-DMAG, inhibits HSP90 activity and blocks multiple signaling pathways, including cell cycle, Akt and HIF pathways. Additionally, the down-regulation of GPX4 protein expression by 17-DMAG and the release of ferric and ferrous ions from gradual degradation of HMPB in the endogenous mild acidic microenvironment in tumors promoted the occurrence of ferroptosis. Importantly, the antitumor effect of 17-DMAG and ferroptosis damage were amplified using photothermal effect of HMPB by accelerating release of ferric and ferrous ions, and reducing HSP90 expression in cells, which induced powerful antitumor effect in vitro and in vivo. This multi-hit therapeutic nanosystem helps provide a novel perspective for solving the predicament of cancer treatment, as well as a promising strategy for design of a novel cancer treatment nanoplatform.

Flash extraction of the active constituents and its antitumor activity from rehmanniae radix, achyranthes bidentatae radix, dioscoreae rhizoma and chrysanthemi flos.

In this study, we applied the Flash extraction (FE) for the first time to the extraction of active ingredients of Sidahuaiyao (including Rehmanniae Radix, Achyranthes Bidentatae Radix, Dioscoreae Rhizoma, and Chrysanthemi Flos), and the content of active ingredients (catalpinoside, ecdysterone, chlorogenic acid and diosgenin) was determined by HPLC, and compared with Soxhlet extraction (SE) and ultrasonic extraction (UE). The results show that under the same solvent ratio, FE is used to extract the largest amount of different active ingredients. Compared with SE and UE, the extraction amount increases by 20.8% -92%. It is demonstrated for the first time that using FE to extract the active ingredients from Sidahuaiyao produced the highest extraction efficiency. In addition, we evaluated the anticancer activities of the main components. Three cancer cells and one normal cells were used to detect the anti-proliferative activity by MTT assay. The results showed that diosgenin had the strongest inhibitory effect on MCF-7 cells with IC50 value of 19.28±0.36µM. In short, we optimized the extraction process of Sidahuaiyao, and evaluated the anti-cancer activity of the main components, which provided a scientific theoretical basis for the application of Sidahuaiyao.

Panaxadiol as a major metabolite of AD-1 can significantly inhibit the proliferation and migration of breast cancer cells: In vitro and in vivo study.

Previous studies have shown that 20 (R)-25-methoxyl-dammarane-3ß, 12ß, 20 triol (AD-1) can inhibit various cancer cell lines. This study aimed to explore the effect and mechanism of AD-1 metabolite M2 (Panaxadiol; PD) on breast cancer cells of nude mice. Five AD-1 metabolites were isolated and identified using various chromatographic techniques. PD was the main component. In vitro results showed that PD could inhibit the proliferation and migration of MDA-MB-231 cells by inducing G1-phase arrest. In addition, PD down-regulated the expression of Cyclin D1, cdk2, cdk4, cdk6, P-p38, and MMP9, and up-regulated p21 and p27. In vivo results showed that PD could effectively reduce the volume, weight, and migration of breast cancer Transcriptomics analyzed 491 differentially expressed genes by GO and KEGG enrichment. RT-PCR verification confirmed that the significant down-regulation of MMP9 was consistent with transcriptomics results. In further research showed that PD regulated the protein expression of P-p38 and MMP9 in MAPK pathway. In summary, in vivo and in vitro studies showed that PD significantly inhibit the occurrence and development of breast cancer, possibly through the MAPK pathway.

Activity Components from Gynostemma pentaphyllum for Preventing Hepatic Fibrosis and of Its Molecular Targets by Network Pharmacology Approach.

Hepatic fibrosis would develop into cirrhosis or cancer without treating. Hence, it is necessary to study the mechanism and prevention methods for hepatic fibrosis. Gynostemma pentaphyllum is a traditional medicinal material with a high medicinal and health value. In this study, nineteen compounds obtained from G. pentaphyllum were qualitative and quantitative by HPLC-FT-ICR MS and HPLC-UV, respectively. Among them, the total content of 19 gypenosides accurately quantified reaches 72.21 mg/g and their anti-proliferation against t-HSC/Cl-6 cells indicated compound 19 performed better activity (IC50: 28.1 ± 2.0 µM) than the other compounds. Further network pharmacology study demonstrated that compound 19 mainly plays an anti-fibrosis role by regulating the EGFR signaling pathway, and the PI3K-Akt signaling pathway. Overall, the verification result indicated that compound 19 appeared to be nontoxic to LO2, was able to modulate the PI3K/Akt signal, led to subG1 cells cycle arrest and the activation of mitochondrial-mediated apoptosis of t-HSC/Cl-6 cells for anti-hepatic fibrosis.

Four new cucurbitane-type triterpenes from Momordica charantia L. with their cytotoxic activities and protective effects on H2O2-damaged pancreatic cells.

Four new cucurbitane-type triterpenes were isolated from the fruit of Momordica charantia L. The structures of the new compounds were identified based on HR-ESI-MS and 1D- and 2D-NMR spectroscopic methods. The cytotoxicity of the isolated compounds was evaluated using three human cancer cell lines, HeLa, Caco2, and U87. Compound 3 exhibited significant cytotoxic activity against HeLa cells with an IC50 value of 11.18 µM. Additionally, the cytoprotective activity of these compounds was determined in vitro against H2O2-induced pancreatic injury. The results revealed that all the compounds obtained possess cytoprotective effects against H2O2-induced injury in MIN6 ß-cells at a concentration of 10 µM.

Synthesis of triterpenoid derivatives and their anti-tumor and anti-hepatic fibrosis activities.

Oleanolic acid (1), ursolic acid (2), hederagenin (3), betulinol (4), betulinic acid (5), and glycyrrhetinic acid (6) are obtained from acorn/licorice industrial wastes with common triterpenoid structure as a model set for esterification. Eight 3,4,5-methoxybenzoyl triterpenoid derivatives (1a-6a), including four new derivatives (1a, 3a-1, 3a-2, and 3a-3), are synthesized by classical procedures. Their antitumor and anti-hepatic fibrosis activities are evaluated on four human tumor cell lines and t-HSC/Cl-6 cells. Derivative 1a shows maximum antiproliferative effects against all cell lines, especially against tumor cells with IC50 values in the range of 5.32-15.23 µM, but does not affect the viability of normal cells. The anti-tumor mechanisms of 1a are also investigated by western blot and docking studies. The 3,4,5-methoxybenzoyl triterpenoids offers an intriguing solution for naturally derived antitumor drugs and may be invaluable for further development of cancer therapy.

Gypensapogenin H from hydrolyzate of total Gynostemma pentaphyllum saponins induces apoptosis in human breast carcinoma cells.

Gypensapogenin H (Gyp H) is a novel dammarane-type triterpene, isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. Our previous work demonstrated that Gyp H exhibited potent growth inhibitory effects on tumor cells. It significantly inhibited the growth of human breast cancer cells (MDA-MB-231), while having low toxicity to normal human breast epithelial cells, MCF-10a. Further mechanistic study demonstrated that Gyp H decreased survival, inhibited proliferation, migration, induced apoptosis and led to cell cycle arrest. For the MDA-MB-231 cell lines, Gyp H increased expression of P21, Bax and cytochrome c, induced PARP cleavage and activated caspases. Gyp H also reduced expression of CDK2/4, CyclinD1, E2F1 and Bcl2, which associated with the cell cycle arrest. Thus, our finding may be useful for understanding the mechanism of action of Gyp H on breast cancer cells and suggest that Gyp H would be a leading agent for the treatment of breast cancer.

Cucurbitane triterpenoids from the fruit of Momordica charantia L. and their anti-hepatic fibrosis and anti-hepatoma activities.

Momordica charantia L. (Cucurbitaceae) is a popular vegetable and traditional folk medicine, that has been used for hundreds of years. In this study, three undescribed cucurbitane-type triterpene glycosides furpyronecucurbitane A, goyaglycoside I and charantagenin F along with nine known compounds were isolated from the immature fruit of Momordica charantia L. Their structures were identified on the basis of extensive 1D, 2D NMR and HRESIMS spectroscopy analysis. All isolated compounds were examined for their anti-hepatic fibrosis activity against murine hepatic stellate cells (t-HSC/Cl-6) and anti-hepatoma activity against two kinds of liver cancer cell lines (HepG2 and Hep3B). Among them, karaviloside III exhibited excellent inhibitory activity against activated t-HSC/Cl-6 cells and cytotoxic activity against Hep3B and HepG2 cell lines with IC50 values of 3.74 ±â€¯0.13, 16.68 ±â€¯2.07 and 4.12 ±â€¯0.36 µM, respectively, which may potential to be developed as a chemotherapy agent for treatment hepatic fibrosis or carcinoma and protection against both diseases.

Synthesis, characterization and cytotoxic activity evaluation of ginsengdiol oxidation and nitrogen hybrid derivatives.

Panaxadiol (PD), a diol-type ginseng saponin, with a dammarane skeleton plays a potential role in the apoptosis of tumor cells. In this study, 28 oxidation and nitrogen hybrid derivatives of PD were synthesized, of which 20 were novel compounds. All the obtained compounds were screened for their cytotoxic activity in six cell lines. As compared with the positive control, some compounds showed better anti-proliferative activities while having much weaker effect on the growth of normal cells. Among them, ring-A fused pyrazoline of PD (1j) displayed impressive cytotoxic activity with IC50 9.62 ± 1.34, 11.65 ± 1.71, and 13.45 ± 1.60 µM against A549, HeLa and 8901 cell lines, respectively. Additionally, compound 2f exhibited the most potent activity with an IC50 value of 8.93 ± 1.11 µM against cell line A549. Therefore, our results indicated that 1j and 2f can be promising lead candidates for further studies.

Polyphenols from Acorn Leaves (Quercus liaotungensis) Protect Pancreatic Beta Cells and Their Inhibitory Activity against α-Glucosidase and Protein Tyrosine Phosphatase 1B.

Acorn leaves, which possess potential pharmacologic effects, are traditionally consumed as food in China. Phytochemical investigations of acorn leaves yielded one new and 25 known polyphenols, and their structures were identified by extensive spectroscopic analysis. Three antidiabetes assays were conducted. Compound 2 considerably increased the survival of pancreatic beta cells by reducing the production of reactive oxygen species and enhancing the activities of superoxide dismutase, catalase, and glutathione in MIN6 cells damaged by H2O2. The preliminary mechanism by which compound 2 protects pancreatic beta cells was through the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 HO-1 pathway. Most of the tested isolates showed strong inhibitory activity against α-glucosidase and protein tyrosine phosphatase 1B. The IC50 values of most compounds were much lower than those of the positive control. The results suggest that polyphenols from acorn leaves are potential functional food ingredients that can be used as antidiabetic agents.

Design, characterization, and in vitro antiproliferative efficacy of gemcitabine conjugates based on carboxymethyl glucan.

Gemcitabine (GEM) is widely used in clinical practice in the treatment of cancer and several other solid tumors. Nevertheless, the antitumor effect of GEM is partially prevented by some limitations including short half life, and lack of tumor localizing. Carboxymethyl glucan (CMG), a carboxymethylated derivative of ß-(1-3)-glucan, shows biocompatibility and biodegradability as well as a potential anticarcinogenic effect. To enhance the antiproliferative activity of GEM, four water soluble conjugates of GEM bound to CMG via diverse amino acid linkers were designed and synthesized. 1H NMR, FT IR, elementary analysis and RP-HPLC chromatography were employed to verify the correct achievement of the conjugates. In vitro release study indicated that conjugates presented slower release in physiological buffer (pH 7.4) than acidic buffer (pH 5.5) mimicking the acidic tumor microenvironment. Moreover, A549, HeLa and Caco-2 cancer cell lines were used to evaluate the in vitro cytotoxicity of conjugates and the results showed that binding GEM to CMG significantly enhanced antiproliferative activity of GEM on A549 cells. Therefore, these conjugates may be potentially useful as a delivery vehicle in cancer therapy and worthy of further study on structure-activity relationship and antiproliferative activity in vitro and in vivo, especially for lung tumor.