Corylin inhibits the progression of Non-small cell lung cancer cells by regulating NF-κB signaling pathway via targeting p65.

BACKGROUND: Lung cancer is characterized by high-risk and high mortality, among which non-small cell lung cancer (NSCLC) conquers a dominant position. Previous studies have reported that corylin has anti-inflammatory, anti-oxidant, and anti-tumor effects; however, its role in NSCLC cells remains unclear. HYPOTHESIS: Corylin inhibits the progression of NSCLC cells. METHODS: A lentivector NF-κB luciferase reporter was constructed by molecular cloning. Corylin was screened and identified as an NF-κB pathway inhibitor by luciferase reporter assay. Corylin inhibited the expression of NF-κB downstream genes, which was detected by qRT-PCR. The effect of corylin on NSCLC cells was detected by colony formation assay, cell apoptosis, cell proliferation, in vitro invasion, and cell scratch assay. Corylin inhibited p65 nuclear translocation and was detected by molecular docking, immunofluorescence assay, and Western blot analysis. RESULTS: We constructed a lentiviral expression vector, containing an NF-κB luciferase reporter and established a stable A549 cell line for its expression. Using this cell line, corylin was screened and identified as an NF-κB pathway inhibitor. It was found that corylin inhibited the expression of NF-κB downstream genes and inhibited the proliferation and migration of NSCLC cells. Meanwhile, it was also found that corylin significantly reversed the increased proliferation of NSCLC cell lines induced by p65 overexpression. Molecular docking analysis showed that corylin could bind to p65 by hydrogen bonding. Further study showed that corylin inhibited the NF-κB signaling pathway by blocking p65 nuclear translocation. CONCLUSIONS: Our study screened and identified corylin as an NF-κB inhibitor and elucidated the molecular mechanism by which corylin inhibits the growth of NSCLC cells. The present study provides a novel strategy for improving the prognosis and treatment of NSCLC patients.

Pharmacological Activity of Quercetin: An Updated Review.

Quercetin, a natural flavonoid compound with a widespread occurrence throughout the plant kingdom, exhibits a variety of pharmacological activities. Because of the wide spectrum of health-promoting effects, quercetin has attracted much attention of dietitians and medicinal chemists. An updated review of the literature on quercetin was performed using PubMed, Embase, and Science Direct databases. This article presents an overview of recent developments in pharmacological activities of quercetin including anti-SARS-CoV-2, antioxidant, anticancer, antiaging, antiviral, and anti-inflammatory activities as well as the mechanism of actions involved. The biological activities of quercetin were evaluated both in vitro and in vivo, involving a number of cell lines and animal models, but metabolic mechanisms of quercetin in the human body are not clear. Therefore, further large sample clinical studies are needed to determine the appropriate dosage and form of quercetin for the treatment of the disease.

[Curative effect of the combined therapy of warm acupuncture at back-shu points of five zang organs and western medicine on depression of yang deficiency pattern and its attenuating effect].

OBJECTIVE: To compare the therapeutic results and the occurrence of adverse reactions of medicine between the combined therapy of warm acupuncture at back-shu points of five zang organs and the western medicine and the simple wes-tern medication, and observe the therapeutic effect and attenuating effect of this combined therapy in treatment on depression of yang deficiency pattern. METHODS: A total of 80 patients with depression of yang deficiency pattern were randomly divided into an observation group and a control group （39 cases/group）. In the control group, escitalopram oxalate tablets were administered orally every day. In the observation group, on the base of the medication as the control group, warm acupuncture therapy was exerted at back-shu points of five zang organs, for 30 min each time, 5 times a week. The duration of treatment was 6 weeks in two groups. Before and after treatment, the scores of Hamilton depression scale (HAMD) and the antidepressant side effect scale (SERS) were evaluated and electroencephalogram (EEG) was detected; and the curative effect was assessed according to HAMD reduction rate in patients of the two groups. RESULTS: After treatment, the HAMD and SERS scores were lower than those before treatment in both groups. Compared with the control group, the HAMD and SERS scores were lower (P<0.05, P<0.01), and the EEG result was improved (P<0.01) in the observation group. The clinical total effective rate of the observation group was 97.43% (38/39), higher than 92.30% (36/39) of the control group (P<0.05). CONCLUSION: The combined therapy of warm acupuncture at back-shu points of five zang organs and western medicine effectively relieves depression of yang deficiency pattern in the patients and its overall therapeutic effect is better than simple western medication, besides, the combined therapy alleviates the adverse reactions induced by simple western medication.

[Impact of abdominal moxibustion in a period of day from 7 am to 9 am on improvement in post-stroke lower limb spasticity and muscle architecture parameter].

OBJECTIVE: To compare the therapeutic effect on post-stroke lower limb spasticity between the combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training and the simple rehabilitation training. METHODS: A total of 100 patients with post-stroke lower limb spasticity were randomized into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 4 cases dropped off ). In the control group, the basic treatment of internal medicine and rehabilitation training of the limbs were adopted. In the observation group, on the basis of the treatment in the control group, at the time zone from 7 am to 9 am, moxibustion on the abdomen with "eight-trigram" moxa box [the central moxa box accurately facing Shenque (CV 8)] was given, lasting for 2 h, once every two days. Both groups were treated for 6 weeks. Separately, before and after treatment, the score of Fugl-Meyer assessment of the lower extremity (FMA-LE) and the grade of modified Ashworth scale (MAS) of ankle joint were evaluated on the affected side in patients of the two groups. Muscle skeleton ultrasound (MSUS) was adopted to determine the first layer muscle thickness (MT) anterior to the tibia, the number of pennation angle (PA) and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side. Besides, after treatment, the therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the score of FMA-LE and the grade of MAS of ankle joint on the affected side were both improved as compared with those before treatment in patients of the two groups (P<0.01, P<0.05). The improvements in the observation group were better than those in the control group (P<0.01, P<0.05). After treatment, MT anterior to the tibia, the number of PA and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side were all increased as compared with before treatment in patients of the two groups (P<0.01). The increase degree in the observation group was larger than that in the control group (P<0.01). The total effective rate was 93.6% (44/47) in the observation group, better than 80.4% (37/46) in the control group (P<0.05). CONCLUSION: The combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training effectively relieves post-stroke lower limb spasticity and improves the limb functions and muscle structure. The total effective rate of this combined treatment is better than that of simple rehabilitation training.

[Effect of jiaotong qiaomai needling technique of acupuncture on the morphology of lower limb muscle based on muscle-skeleton ultrasound measurement in patients with post-stroke strephenopodia].

OBJECTIVE: To evaluate the therapeutic effect on post-stroke strephenopodia treated with jiaotong qiaomai (harmonizing the heel vessel) needling technique of acupuncture. METHODS: A total of 64 patients were randomized into an observation group (30 cases included, 2 cases dropped off) and a control group (30 cases included, 2 cases dropped off). In the control group, the routine needling technique of acupuncture and rehabilitation exercise were provided. In the observation group, on the base of the therapeutic regimen as the control group, the jiaotong qiaomai needling technique of acupuncture was added. Fengchi (GB 20), Rangu (KI 2), Zhaohai (KI 6) on the affected side and Fengfu (GV 16) were selected. The treatment was given once daily, 5 times a week, for 4 weeks totally in either group. Separately, before treatment, in 2 weeks and 4 weeks of treatment, the strephenopodia angle was measured and Holden functional ambulation classification (FAC) was evaluated in the patients. Additionally, before treatment and in 4 weeks of treatment, the muscle-skeleton ultrasound was adopted to measure the thickness of anterior tibia muscle and posterior tibia muscle in the resting state of the patients. RESULTS: The strephenopodia angle and Holden FAC were all improved after 4-week treatment in the two groups as compared with those before treatment (P<0.01, P<0.05), and the results in the observation group were better than those in the control group (P<0.01, P<0.05). Before treatment, the thickness of anterior tibia muscle and posterior tibia muscle on the healthy side was higher than that on the affected side in the patients of the two groups (P<0.05). After treatment, the thickness of anterior tibia muscle and posterior tibia muscle on the affected side was increased as compared with that before treatment in the two groups (P<0.01, P<0.05). The thickness on the healthy side was similar before and after treatment in the observation group (P>0.05), and it was increased on the healthy side after treatment as compared with that before treatment in the control group (P<0.05). After treatment, the thickness of anterior tibia muscle and posterior tibia muscle on the affected side was similar to that on the healthy side in the two groups (P>0.05), and the thickness on the affected side in the observation group was higher than that in the control group after treatment (P<0.05). CONCLUSION: The jiaotong qiaomai needling technique of acupuncture effectively improves the strephenopodia angle and ambulation function, as well as the morphology of anterior tibia muscle and posterior tibia muscle in the patients with post-stroke strephenopodia.

[Effect of electronic moxibustion on activity of parapharyngeal wall in patients with achalasia of cricopharyngeus muscle after stroke based on musculoskeletal ultrasound].

OBJECTIVE: To observe the clinical effect of electronic moxibustion on dysphagia in patients with achalasia of cricopharyngeus muscle after stroke. METHODS: Sixty patients with dysphagia of achalasia of cricopharyngeus muscle were randomly divided into an observation group and a control group, 30 cases in each group. One patient in the observation group and 2 cases in the control group dropped off. The patients in the control group were treated with routine medical treatment, acupuncture treatment and swallowing rehabilitation training; the patients in the observation group were additionally treated with electronic moxibustion at Lianquan (CV 23), Tiantu (CV 22), Tianding (LI 17) and Futu (LI 18), 30 min each treatment. Both groups were treated 5 times a week for 4 weeks. The musculoskeletal ultrasound (MSUS) was applied to test the activity of parapharyngeal wall and the dysphagia score of Ichiro Fujishima was compared before and after 4-week treatment. RESULTS: After treatment, the activity of the parapharyngeal wall and the dysphagia score of Ichiro Fujishima were increased in both groups (P<0.01, P<0.05). The changes of activity of parapharyngeal wall and dysphagia score of Ichiro Fujishima in the observation group were greater than the control group (P<0.05, P<0.01). CONCLUSION: Electronic moxibustion can improve the impaired swallowing function and reconstruct the normal swallowing process.

Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway.

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

Co-delivery of Bee Venom Melittin and a Photosensitizer with an Organic-Inorganic Hybrid Nanocarrier for Photodynamic Therapy and Immunotherapy.

Photodynamic therapy (PDT) is a clinical cancer treatment modality based on the induction of therapeutic reactive oxygen species (ROS), which can trigger immunogenic cell death (ICD). With the aim of simultaneously improving both PDT-mediated intracellular ROS production and ICD levels, we designed a serum albumin (SA)-coated boehmite ("B"; aluminum hydroxide oxide) organic-inorganic scaffold that could be loaded with chlorin e6 (Ce6), a photosensitizer, and a honey bee venom melittin (MLT) peptide, denoted Ce6/MLT@SAB. Ce6/MLT@SAB was anchored by a boehmite nanorod structure and exhibited particle size of approximately 180 nm. Ce6/MLT@SAB could significantly reduce hemolysis relative to that of free MLT, while providing MLT-enhanced PDT antitumor effects in vitro. Compared with Ce6@SAB, Ce6/MLT@SAB improved Ce6 penetration of cancer cells both in vitro and in vivo, thereby providing enhanced intracellular ROS generation with 660 nm light treatment. Following phototreatment, Ce6/MLT@SAB-treated cells displayed significantly improved levels of ICD and abilities to activate dendritic cells. In the absence of laser irradiation, multidose injection of Ce6/MLT@SAB could delay the growth of subcutaneous murine tumors by more than 60%, compared to controls. When combined with laser irradiation, a single injection and phototreatment with Ce6/MLT@SAB eradicated one-third of subcutaneous tumors in treated mice. The addition of an immune checkpoint blockade to Ce6/MLT@SAB phototreatment further augmented antitumor effects, generating increased numbers of CD4+ and CD8+ T cells in tumors with concomitant reduction of myeloid-derived suppressor cells.

DNA-hosted copper nanoclusters/graphene oxide based fluorescent biosensor for protein kinase activity detection.

A novel fluorescent biosensor for protein kinase activity (PKA) detection was designed by applying double-strands DNA-hosted copper nanoclusters (dsDNA-CuNCs) and graphene oxide (GO). One DNA strand of the dsDNA consisted of two domains, one domain can hybridize with another complementary DNA strand to stabilize the fluorescent CuNCs and another domain was adenosine 5'-triphosphate (ATP) aptamer. ATP aptamer of the dsDNA-CuNCs would be spontaneously absorbed onto the GO surface through π-π stacking interactions. Thus GO can efficiently quench the fluorescence (FL) of dsDNA-CuNCs through fluorescence resonance energy transfer (FRET). In the present of ATP, ATP specifically combined with ATP aptamer to form ATP-ATP aptamer binding complexes, which had much less affinity to GO, resulting in the fluorescence recovery of the system. Nevertheless, in the presence of PKA, ATP could be translated into ADP and ADP could not combine with ATP aptamer resulting in the fluorescence quenching of dsDNA-CuNCs again. According to the change of the fluorescence signal, PKA activity could be successfully monitored in the range of 0.1-5.0 U mL-1 with a detection limit (LOD) of 0.039 U mL-1. Besides, the inhibitory effect of H-89 on PKA activity was studied. The sensor was performed for PKA activity detection in cell lysates with satisfactory results.

Hydro-dam - A nature-based solution or an ecological problem: The fate of the Tonlé Sap Lake.

Recent proliferation of hydro-dams was one of the nature-based solutions to meet the increasing demand for energy and food in the Lower Mekong River Basin (LMRB). While construction of these hydro-dams generated some hydropower and facilitated expansion of irrigated lands, it also significantly altered the basin-wide hydrology and subsequently impacted wetland ecosystems. Unintended adverse consequences of ecosystem services from lakes and wetlands offset the intended gains in hydroelectricity and irrigated agriculture. The trade-offs between gains in energy and food production and losses in aquatic ecosystem services were perceived to be significant but knowledge of the magnitude, spatial extent, and type of ecosystem services change is lacking and, therefore, the question whether the hydro-dam is an optimized solution or a potential ecological problem remains unanswered. In this study, as the first step to answer this question and using the Tonlé Sap Lake as an example, we quantified one of the impacts of hydro-dams on lake ecosystem's phenology in terms of open water area, a critical ecological characteristic that affects lake systems' fish production, biodiversity, and livelihoods of the local communities. We used the MODIS-NDVI time series, forecast function and the Mann-Kendall trend test method to first quantify the open water area, analyzed its changes over time, and then performed correlation analysis with climate variables to disentangle dam impacts. The results showed reduced hydro-periods, diminishing lake seasonality and a declining trend in Tonlé Sap Lake open water area over the past 15 years. These changes were insignificantly related to climatic influence during the same period. It is concluded that basin-wide hydro-dam construction and associated agricultural irrigation were deemed to be the primary cause of these ecological changes. Further analyses of changes in the lake's ecosystem services, including provision and cultural services, need to be carried out in order to have a holistic understanding of the trade-offs brought by the hydro-dam proliferation as a solution to the emerging energy and food demand in the LMRB.

Evidence-based novel changes in prevalence and symptom characteristics of spleen deficiency syndrome in persons of varied health status and different ages: a cross-sectional observational study.

Deficiency of the organs is a vital pathophysiologic characteristic in the elderly. A core TCM aging theory is known as aging caused by spleen deficiency syndrome (SDS) that can be found in ancient and modern literature. The key objectives of this study were to establish a full-scale trial to evaluate the prevalence, symptom severity, frequency, and distribution of SDS in different age groups as related to health status (healthy, subhealthy, and chronic disease) to elucidate the role of spleen deficiency in the aging process and deterioration of health status. This cross-sectional observational study was conducted in 4 hospitals in China. 1390 participants aged 20-79 were interviewed by investigators who completed questionnaires recording prevalence, severity, and frequency of symptoms as well as other relevant information. The results revealed that prevalence and symptom characteristics of SDS showed regularities with increasing age and deteriorating health status. It supports the TCM concept that spleen deficiency is an important mechanism of aging, subhealth, and chronic diseases. Early recognition of the warning signs and symptoms of SDS may lead to intervention and even prevention strategies for subhealth and chronic diseases as well as promotion of healthy aging.