Investigation of Molecular Mechanisms Involved in Sensitivity to the Anti-Cancer Activity of Costunolide in Breast Cancer Cells.

Costunolide (CTL), an active compound isolated from Saussurea lappa Clarke and Laurus nobilis L, has been shown to induce apoptosis via reactive oxygen species (ROS) generation in various types of cancer cells. However, details of molecular mechanisms underlying the difference in sensitivity of cancer cells to CTL are still largely unknown. Here, we tested the effect of CTL on the viability of breast cancer cells and found that CTL had a more efficient cytotoxic effect against SK-BR-3 cells than MCF-7 cells. Mechanically, ROS levels were significantly increased upon CTL treatment only in SK-BR-3 cells, which leads to lysosomal membrane permeabilization (LMP) and cathepsin D release, and subsequent activation of the mitochondrial-dependent intrinsic apoptotic pathway by inducing mitochondrial outer membrane permeabilization (MOMP). In contrast, treatment of MCF-7 cells with CTL activated PINK1/Parkin-dependent mitophagy to remove damaged mitochondria, which prevented the elevation of ROS levels, thereby contributing to their reduced sensitivity to CTL. These results suggest that CTL is a potent anti-cancer agent, and its combination with the inhibition of mitophagy could be an effective method for treating breast cancer cells that are less sensitive to CTL.

Epidemiology and Seasonal Variation of Ménière's Disease: Data from a Population-Based Study.

INTRODUCTION: Ménière's disease (MD) is a disease of the inner ear. In Asian countries, there is one previous epidemiologic study that used a retrospective survey of a specific district. Previous studies have demonstrated that weather variables are strongly associated with symptom aggravation in MD. However, no study has reported on seasonal variation of MD. METHODS: We conducted a retrospective population-based study using the Korean national health insurance claims database (NHICD). In the present study, the prevalence and incidence of MD from 2013 to 2017 were calculated. Prevalence and incidence of MD according to sex, age group, and monthly incidence are presented. Seasonal incidence was calculated for four seasons. The seasonal average humidity and atmospheric pressure were also calculated. RESULTS: The incidence rate of MD showed a rapid yearly increase from 2013 to 2017 in Korea. The prevalence and incidence rate by age group continued to increase up to the 70 year olds. The female-to-male ratio was 2.17. The seasonal incidence of MD was relatively high in summer and autumn and relatively low in winter and spring; however, there were no significant differences. DISCUSSION/CONCLUSIONS: The rapid progression to an aging society, increase in medical accessibility, and lifestyle changes could be the reasons for the elevation of the incidence rate in the Korean population. Consistent with a previous study, the incidence of MD was higher in seasons with high humidity and low atmospheric pressure; however, there were no significant differences. Further studies about the relationship between diet and MD, seasonality of MD with long-term analysis, and investigating the underlying mechanisms connecting weather and MD are needed.

The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo.

BACKGROUND: Jawoongo is an herbal mixture used in traditional medicine to treat skin diseases. This study aimed to investigate whether Jawoongo ameliorates Atopic dermatitis (AD)-like pathology in mice and to understand its underlying cellular mechanisms. METHODS: AD was induced by 2, 4-Dinitrocholrlbenzene (DNCB) in BALB/c mice. Treatment with Jawoongo was assessed to study the effect of Jawoongo on AD in mice. Histological Analysis, blood analysis, RT-PCR, western blot analysis, ELISA assay and cell viability assay were performed to verify the inhibitory effect of Jawoongo on AD in mice. RESULTS: We found that application of Jawoongo in an ointment form on AD-like skin lesions on DNCB-exposed BALB/c mice reduced skin thickness and ameliorated skin infiltration with inflammatory cells, mast cells and CD4+ cells. The ointment also reduced the mRNA levels of IL-2, IL-4, IL-13 and TNF-α in the sensitized skin. Leukocyte counts and the levels of IgE, IL-6, IL-10 and IL-12 were decreased in the blood of the DNCB-treated mice. Furthermore, studies on cultured cells demonstrated that Jawoongo exhibits anti-inflammatory activities, including the suppression of proinflammatory cytokine expression, nitric oxide (NO) production, and inflammation-associated molecule levels in numerous types of agonist-stimulated innate immune cell, including human mast cells (HMC-1), murine macrophage RAW264.7 cells, and splenocytes isolated from mice. CONCLUSION: These findings indicate that Jawoongo alleviates DNCB-induced AD-like symptoms via the modulation of several inflammatory responses, indicating that Jawoongo might be a useful drug for the treatment of AD.

Comparative effects of artemisia vulgaris and charcoal moxa stimulating Zhongwan (CV 12) on body temperature in healthy participants: a cross-over single-blind randomized study.

OBJECTIVE: To evaluate the efficacy, safety, satisfaction, discomfort and patient preference of moxa cones of artemisia vulgaris and charcoal moxa. METHODS: This comparative study of moxibustion treatment with Artemisia vulgaris and charcoal moxa cone stimulating Zhongwan (CV 12) is a cross-over single-blinded, randomized clinical trial. A total of 40 healthy subjects (24 males and 16 females) participated in this study. Two subjects dropped out of the trial. Thirty-eight subjects were treated with Artemisia vulgaris and charcoal moxa cones for 30 min in a cross-over design. After treatment, the patients underwent a 30 minute waiting period, and then the temperatures at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4) were measured using digital infrared thermal imaging. RESULTS: After the use of Artemisia vulgaris moxa, the patients' body temperatures were slightly lowered at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After the use of charcoal moxa, the patients' body temperatures were somewhat increased at Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After Artemisia vulgaris moxa use, the body temperature difference between Zhongwan (CV 12) and Guanyuan (CV 4) was significantly increased. After charcoal moxa use, the body temperature difference between Tanzhong (CV 17) and Zhongwan (CV 12) was significantly decreased in males and in the whole group. This change was caused by the difference in the moxibustion type and by gender differences. CONCLUSION: This pilot study found that moxibustion did not raise the body temperature, but temperature differences between acupoints were affected. Further large-scale randomized controlled trials are needed for the effect of moxibustion on body temperature.

Synergistic and Additive Effects of Herbal Medicines in Combination with Chemotherapeutics: A Scoping Review.

BACKGROUND: Natural products are increasingly gaining interest as potential new drug candidates for cancer treatment. Herbal formula, which are combinations of several herbs, are primarily used in East Asia and have a long history of use that continues today. Recently, research exploring the combination of herbal formulas and chemotherapy for cancer treatment has been on the rise. METHODS: This study reviewed research on the co-administration of herbal formulas and chemotherapy for cancer treatment. The databases PubMed, Embase, and Cochrane Library were used for article searches. The following keywords were employed: "Antineoplastic agents," "Chemotherapy," "Phytotherapy," "Herbal medicine," "Drug synergism," and "Synergistic effect." The selection process focused on studies that investigated the synergistic interaction between herbal formulas and chemotherapeutic agents. RESULTS: Among the 30 studies included, 25 herbal formulas and 7 chemotherapies were used. The chemotherapy agents co-administered included cisplatin, 5-fluorouracil, docetaxel, doxorubicin, oxaliplatin, irinotecan, and gemcitabine. The types of cancer most frequently studied were lung, breast, and colon cancers. Most studies evaluating the anticancer efficacy of combined herbal formula and chemotherapy treatment were conducted in vitro or in vivo. DISCUSSION: Most studies reported synergistic effects on cytotoxicity, apoptosis, and tumor growth inhibition. These effects were found to be associated with cell cycle arrest, anti-angiogenesis, and gene expression regulation. Further studies leading to clinical trials are required. Clinical experiences in East Asian countries could provide insights for future research.

KM110329 in adult patients with atopic dermatitis: a randomised, double-blind, placebo-controlled, multicentre trial--study protocol.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease with a high prevalence rate and a large socioeconomic cost. There are many treatments for atopic dermatitis, such as antihistamine, tacrolimus and corticosteroids. However, due to concern about the adverse effects, many patients seek alternative treatments. In this context, natural products are gaining interest. KM110329 is a functional food consisting of four herbs that are beneficial to skin health. The purpose of this study is to assess the efficacy and safety of KM110329 for atopic dermatitis. METHODS/DESIGN: This study is a randomised, double-blind, placebo-controlled and multicentre trial of KM110329. For this study, we will recruit 66 atopic dermatitis patients of both sexes, with ages ranging from 18 to 65, from three university hospitals. The participants will receive either KM110329 or a placebo twice a day for 8 weeks. The primary end point will be a change in the scoring atopic dermatitis (SCORAD) index. The secondary end points will include changes to the dermatology life quality index (DLQI) and transepidermal water loss (TEWL), among others. The outcomes will be measured at every visit. The study will be continued for 8 weeks and will include five visits with each subject (at screening and at 0, 1, 4 and 8 weeks). DISCUSSION: This trial will provide research methodologies for evaluate clinical efficacy and safety of KM110329 in adult patients with atopic dermatitis. In addition, we will evaluate the changes in the general skin health status and quality of life. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01692093.

Natural Products as New Approaches for Treating Bladder Cancer: From Traditional Medicine to Novel Drug Discovery.

Bladder cancer (BC) is a heterogeneous disease that a tumor develops in the bladder lining and in some cases, the bladder muscle. Chemotherapy and immunotherapy are commonly used to treat bladder cancer. However, chemotherapy can cause burning and irritation in the bladder while BCG immunotherapy, which is the main type of intravesical immunotherapy for bladder cancer, can also cause burning in the bladder and flu-like symptoms. Thus, drugs originating from natural products have attracted much attention due to the reports that they have anti-cancer properties with low adverse effects. In this study, eighty-seven papers that dealt with natural products preventing or treating bladder cancer were reviewed. The studies were classified into the following mechanism: 71 papers on cell death, 5 papers on anti-metastasis, 3 papers on anti-angiogenesis, 1 paper on anti-resistance, and 7 papers on clinical trials. Most of the natural products that induced apoptosis up-regulated proteins such as caspase-3 and caspase-9. Regarding anti-metastasis, MMP-2 and MMP-9 are regulated frequently. Regarding anti-angiogenesis, HIF-1α and VEGF-A are down-regulated frequently. Nevertheless, the number of papers regarding anti-resistance and clinical trial are too few, so more studies are needed. In conclusion, this database will be useful for future in vivo studies of the anti-bladder cancer effect of natural products, in the process of selecting materials used for the experiment.

SH003 Causes ER Stress-mediated Apoptosis of Breast Cancer Cells via Intracellular ROS Production.

BACKGROUND/AIM: Breast cancer is one of the most common cancers in women all over the world and new treatment options are urgent. ER stress in cancer cells results in apoptotic cell death, and it is being proposed as a new therapeutic target. SH003, a newly developed herbal medicine, has been reported to have anti-cancer effects. However, its molecular mechanism is not yet clearly defined. MATERIALS AND METHODS: Microarray was performed to check the differential gene expression patterns in various breast cancer cell lines. Cell viability was measured by MTT assays to detect cytotoxic effects. Annexin V-FITC and 7AAD staining, TUNEL assay and DCF-DA staining were analyzed by flow cytometry to evaluate apoptosis and ROS levels, respectively. Protein expression was examined in SH003-breast cancer cells using immunoblotting assays. The expression of C/EBP Homologous Protein (CHOP) mRNA was measured by real-time PCR. The effects of CHOP by SH003 treatment were investigated using transfection method. RESULTS: Herein, we investigated the molecular mechanisms through which SH003 causes apoptosis of human breast cancer cells. Both cell viability and apoptosis assays confirmed the SH003-induced apoptosis of breast cancer cells. Meanwhile, SH003 altered the expression patterns of several genes in a variety of breast cancer cell lines. More specifically, it upregulated gene sets including the response to unfolded proteins, independently of the breast cancer cell subtype. In addition, SH003-induced apoptosis was due to an increase in ROS production and an activation of the ER stress-signaling pathway. Moreover, CHOP gene silencing blocked SH003-induced apoptosis. CONCLUSION: SH003 causes apoptosis of breast cancer cells by upregulating ROS production and activating the ER stress-mediated pathway. Thus, our findings suggest that SH003 can be a potential therapeutic agent for breast cancer.

Synergistic effects of natural products in combination with anticancer agents in prostate cancer: A scoping review.

Background: Prostate cancer is the second most common cancer in men and has the fourth highest mortality among men worldwide. Different combination therapies for cancer are being tested, and among them, the integration of natural products is increasing. This study reviews research on the combination of anticancer drugs and natural products for the treatment of prostate cancer and suggests future directions in this field. Methods: Articles were identified by searching the PubMed, Embase, and Cochrane Library databases. Search keywords included the following: "Antineoplastic agents," "Anticancer drug," "Phytotherapy," "Natural product," "Drug synergism," and "Synergistic effect". The selection process focused on whether the differences in efficacy of anticancer drugs were evaluated when combined with natural products. Results: Nineteen studies were included. All 19 studies evaluated efficacy in vitro, as well as 10 in vivo. There were 13 studies on a single compound extracted from natural products, three studies on mushroom and herb extracts, and three studies on herbal medicines consisting of three herbs, and a dietary supplement containing 10 herbs. Cancer cell lines used were PC-3 in nine studies, LNCaP in six studies, C4-2 in five studies, DU-145 in four studies, and 22Rv1 in two studies. Anti-cancer drugs co-administered were as follows: docetaxel in nine studies, doxorubicin and enzalutamide in three studies, paclitaxel and suberoylanilide hydroxamic acid in two studies, and cisplatin, vincristine, and bicalutamide in one study each. Conclusion: Although prostate cancer is prevalent worldwide, there are relatively few studies on the use of natural products with anticancer agents as treatment. Since it has reported that the efficacy of anticancer drugs is enhanced by coadministration of natural products, it is necessary to conduct further studies on this.

The Effect of Ginger and Its Sub-Components on Pain.

Zingiber officinale Roscoe (ginger) has long been used as an herbal medicine to treat various diseases, and its main sub-components, [6]-gingerol and [6]-shogaol, were also reported to have anti-inflammatory, anti-oxidant, and anti-tumor effects. However, their effects on various types of pain and their underlying mechanisms of action have not been clearly analyzed and understood yet. Thus, in this review, by analyzing 16 studies that used Z. officinale, [6]-gingerol, and [6]-shogaol on mechanical, spontaneous and thermal pain, their effects and mechanisms of action have been analyzed. Pain was induced by either nerve injury or chemical injections in rodents. Nine studies analyzed the analgesic effect of Z. officinale, and four and three studies focused on [6]-gingerol and [6]-shogaol, respectively. Seven papers have demonstrated the underlying mechanism of action of their analgesic effects. Studies have focused on the spinal cord and one on the dorsal root ganglion (DRG) neurons. Involvement and change in the function of serotonergic receptors (5-HT1A, B, D, and 5A), transient receptor potential vanilloid 1 (TRPV1), N-methyl-D-aspartate (NMDA) receptors, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), histone deacetylase 1 (HDAC1), voltage-gated sodium channel 1.8 (Nav1.8), substance P (SP), and sciatic nerve's morphology have been observed.

Global Trends of Nutrition in Cancer Research: A Bibliometric and Visualized Analysis Study over the Past 10 Years.

The increasing application of nutrition in cancer management has attracted a great deal of research interest in recent decades. Nutritional therapies, interventions, and assessments were known to have positive effects on reducing side effects from cancer therapy. In order to identify the global research output for nutrition in cancer research, a bibliometric analysis during the past 10 years was conducted to evaluate the current status of trends, gaps, and research directions as no bibliometric studies have been conducted regarding nutrition and cancer. After the data collection, a total of 1521 articles were chosen for this bibliometric study. The visualization analysis was performed with VOSviewer. The number of publications has grown continuously since a substantial spark was identified in 2019. The majority of the authors' affiliations were in European countries. Four cancer types were recognized among the top 10 author keywords; they were breast cancer, head and neck cancer, colorectal cancer, and gastric cancer. The Nutrients journal was the most popular among the authors as the journal published 195 articles related to the topic. In conclusion, providing evidence-based nutritional solutions for various types of cancer is essential to nutrition and cancer research. Since it is presumed to have a growing number of cancer patients worldwide with the aging population, it is vital to continuously generate research finding effective nutrition therapies for cancer patients.

North Korean arrivals' medical service usage in South Korea, 2015-2019.

This study retrospectively reviews the medical service usage data of North Korean arrivals collected from 2015 to 2019. The purpose of this study is to understand the medical use status of North Korean arrivals and to design health policies for them. We reviewed 32,653 medical records of North Korean arrivals who visited the National Medical Center as outpatients and inpatients during a 5-year period. Among 1453 patients with an average age of 46.7 years, we found that among the treated patients, there were many women in their 40s and 50s who complained of psychiatric disorders. The most frequently visited department was psychiatry. The most frequently diagnosed disorder was unspecified depression. 88% of patients utilized Medical Care assistance type 1, which means that they are medical aid beneficiaries because they are usually in difficult economic circumstances. Medical examination and treatment fees of North Korean arrivals increased in general, and older patients paid more. Among North Korean arrivals, middle-aged women and mentally ill patients showed high medical needs. This study recommends that the government provide policy support to North Korean arrivals for professional psychiatric treatment and improvement of medical access. We also expect these results to be applied to the health problems of other refugees.

Qigong and Tai Chi on Human Health: An Overview of Systematic Reviews.

Qigong and Tai chi are traditional methods of physical and mental training and exercises in East Asia. Their health-promoting effects against various diseases have been studied for a long time, and they have been the subject of many clinical trials and systematic reviews (SRs). The present study aimed to comprehensively evaluate all published SRs on Qigong and Tai chi and to summarize the supporting evidence. The following databases were searched: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Research Information Sharing Service, and Korean Studies Information Service System. The selection and extraction processes were performed by two independent reviewers, and a qualitative synthesis was conducted. There were 58 SRs of randomized controlled trials on Qigong and Tai chi. There have been many studies on patients with cardiovascular diseases and different cancers, and a number of other studies in which mobility, quality of life, blood lipids, and blood pressure were outcome measurements. Thus, Qigong and Tai chi for various diseases and medical conditions have been accumulated. Based on current evidence, the number of publications of Qigong and Tai chi-related articles showed an increasing trend, and most of them were performed in China. Qigong and Tai chi have shown beneficial effects in different age groups and health conditions, including decreasing blood lipid level, reducing blood pressure, facilitating mobility, preventing falls, and improving overall quality of life.

Natural Products for Liver Cancer Treatment: From Traditional Medicine to Modern Drug Discovery.

Primary liver cancer was the seventh most diagnosed cancer and the second leading cause of cancer death with about 906,000 cases and 830,000 deaths, respectively, in 2020. Conventional treatment for liver cancer, such as transarterial chemoembolization (TACE) or sorafenib, has limitations in that there is the recurrence of cancer, drug inefficacy, and adverse effects. Traditional medicine and natural products of several regions including Korea, China, Europe, North America, India, and the Middle East have attracted a lot of attention since they have been reported to have anticancer effects with low adverse effects. In this review, several in vivo studies on the effects of natural compounds on liver cancer and clinical trials approving their therapeutic benefits were selected and discussed. As a result of the analysis of these studies, the effects of natural compounds were classified into a few mechanisms: apoptosis, anti-metastasis, and antiangiogenesis. In addition, medications including natural products in clinical trials were observed to exhibit improvements in various liver cancer symptoms and patients' survival rates. This study presents findings suggestive of the anticancer potential of natural products and their properties in relieving related symptoms.

Factors influencing use of conventional and traditional Korean medicine-based health services: a nationwide cross-sectional study.

BACKGROUND: In Korea, conventional medicine (CM) and traditional Korean medicine (KM) are run as a dual healthcare system; however, the backgrounds and characteristics of the users of both medical services have not yet been compared. This study aimed to identify the differences in factors determining the use of CM and KM health services. METHODS: A secondary data analysis of a nationwide cross-sectional survey was conducted in this study. The Survey on the Experience with Healthcare Services 2017 asked participants about their most recent outpatient visit to a health service. Initially, a descriptive analysis was performed on respondents who visited the CM or KM health service in the last 12 months. Then, logistic regression analysis using Andersen's behavioral model was performed, to identify the factors affecting health service selection, by classifying demographic variables into predisposing, enabling, and need factors. Respondents who replied they did not frequently use CM/KM and those with missing data were excluded. RESULTS: Of the total 11,098 respondents, 7,116 (64.1%) reported to have used CM/KM: 2,034 (18.3%), 4,475 (40.3%), and 607 (5.5%) for hospital CM, clinic CM, and KM, respectively. In logistic regression analysis, of the 2,723 (24.5%) respondents analyzed, 822 (7.4%) went to a hospital, 1,689 (15.2%) to a clinic, and 212 (1.9%) opted for KM service. Respondents with a higher number of chronic diseases were less likely to use KM (one disease, odds ratio: 0.52, 95% confidence interval: 0.36-0.76; two diseases: 0.51, 0.31-0.85; three to five diseases: 0.26, 0.10-0.69). Respondents with a high income were likely to go to the hospital (4Q vs. 1Q: 1.92, 1.35-2.72) and less likely to go to the clinic (4Q vs. 1Q: 0.49, 0.35-0.68). CONCLUSIONS: Significant differences were observed on the enabling factor (income) for CM and need factors (number of chronic diseases) for KM. Our analysis suggests that through the healthcare policy, we should consider stratifying user backgrounds and needs for each medical service.

[6]-Shogaol Attenuates Oxaliplatin-Induced Allodynia through Serotonergic Receptors and GABA in the Spinal Cord in Mice.

Although oxaliplatin is a well-known anti-cancer agent used for the treatment of colorectal cancer, treated patients often experience acute cold and mechanical allodynia as side effects. Unfortunately, no optimal treatment has been developed yet. In this study, [6]-shogaol (10 mg/kg, i.p.), which is one of the major bioactive components of Zingiber officinale roscoe (Z. officinale), significantly alleviated allodynia induced by oxaliplatin (6 mg/kg, i.p.) injection. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. The analgesic effect of [6]-shogaol was blocked by the intrathecal injection of 5-HT1A, 5-HT3, and GABAB receptor antagonists, NAN-190 (1 µg), MDL-72222 (15 µg), and CGP 55845 (10 µg), respectively. Furthermore, oxaliplatin injection lowered the GABA concentration in the superficial laminae of the spinal dorsal horn, whereas [6]-shogaol injection significantly elevated it. The GAD (glutamic acid decarboxylase) 65 concentration also increased after [6]-shogaol administration. However, pre-treatment of NAN-190 completely inhibited the increased GABA induced by [6]-shogaol in the spinal dorsal horn, whereas MDL-72222 partially blocked the effect. Altogether, these results suggest that [6]-shogaol could attenuate oxaliplatin-induced cold and mechanical allodynia through 5-HT1A and 5-HT3 receptor antagonists located in the GABAergic neurons in the spinal dorsal horn in mice.

State of the Art and Future Implications of SH003: Acting as a Therapeutic Anticancer Agent.

Cancer ranks as the first leading cause of death globally. Despite the various types of cancer treatments, negative aspects of the treatments, such as side effects and drug resistance, have been a continuous dilemma for patients. Thus, natural compounds and herbal medicines have earned profound interest as chemopreventive agents for reducing burden for patients. SH003, a novel herbal medicine containing Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, showed the potential to act as an anticancer agent in previous research studies. A narrative review was conducted to present the significant highlights of the total 15 SH003 studies from the past nine years. SH003 has shown positive results in both in vivo and vitro studies against various types of cancer cells; furthermore, the first clinical trial was performed to identify the maximum tolerated dose among solid cancer patients. So far, the potential of SH003 as a chemotherapeutic agent has been well-documented in research studies; continuous work on SH003's efficacy and safety is required to facilitate better cancer patient care but is part of the knowledge needed to understand whether SH003 has the potential to become a pharmaceutical.

Use of traditional, complementary and alternative medicine in nine countries: A cross-sectional multinational survey.

OBJECTIVES: Traditional, complementary, and alternative medicine (TC&AM) play an exceptional role in health care around the world as many patients has sought a holistic approach. SETTING: In this study, a multinational survey was developed and administered to obtain experience, attitude, and promotion information with regard to the international use of TC&AM among nine countries: Germany, United States, Japan, China, Malaysia, Vietnam, Russia, Kazakhstan, and United Arab Emirates (UAE). The survey was administered via online to members of SurveyMonkey Audience, a proprietary panel of respondents who were recruited from a diverse population worldwide. RESULTS: A total of 1071 participants has completed the survey. The participants were in favor of the treatments and therapies as well as expressed positive attitudes and also have used herbal medicine treatment more than acupuncture therapy and also used the modalities to promote metabolism rather than treating musculoskeletal diseases. Moreover, participants mentioned that TC&AM should be applied for treating and managing infectious diseases, such as COVID-19. Additionally, participants recommended using Facebook channel to promote its treatments and therapies. CONCLUSION: Based on the results, this study provides initial insights on TC&AM that may influence the non-users globally and perhaps inspire a need for further research including more countries in different continents.

Recent advances in respiratory diseases: Dietary carotenoids as choice of therapeutics.

A group of bioactive, isoprenoid pigments known as carotenoids is mostly present in fruits and vegetables. Carotenoids are essential for the prevention of physiological issues, which makes maintaining excellent health easier. They are effective functional ingredients with potent health-promoting properties that are widely present in our food and linked to a decrease in the prevalence of chronic diseases, including respiratory diseases. Respiratory infections are the primary cause of death and life-threatening conditions globally, wreaking havoc on the global health system. People rely on dietary sources of carotenoids to reduce a plethora of respiratory diseases such as chronic obstructive pulmonary disease (COPD), lung cancer, asthma, and so on. Carotenoids have received a lot of interest recently in several parts of the world due to their therapeutic potential in altering the pathogenic pathways underlying inflammatory respiratory diseases, which may improve disease control and have beneficial health benefits. This review aimed to provide a thorough understanding of the therapeutic potential of dietary carotenoids in the treatment of respiratory diseases and to identify possible candidates for novel therapeutic development.

BK002 Induces miR-192-5p-Mediated Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulation of PI3K/CHOP.

BK002 consists of Achyranthes japonica Nakai (AJN) and Melandrium firmum Rohrbach (MFR) that have been used as herbal medicines in China and Korea. AJN and MFR have been reported to have anti-inflammatory, anti-oxidative, and anti-cancer activities, although the synergistic targeting multiple anti-cancer mechanism in castration-resistant prostate cancer (CRPC) has not been well reported. However, the drug resistance and transition to the androgen-independent state of prostate cancer contributing to CRPC is not well studied. Here, we reported that BK002 exerted cytotoxicity and apoptosis in CRPC PC3 cell lines and prostate cancer DU145 cell lines examined by cytotoxicity, western blot, a LIVE/DEAD cell imaging assay, reactive oxygen species (ROS) detection, quantitative real-time polymerase chain reaction (RT-PCR), and transfection assays. The results from our investigation found that BK002 showed more cellular cytotoxicity than AJN and MFR alone, suggesting that BK002 exhibited potential cytotoxic properties. Consistently, BK002 increased DNA damage, and activated p-γH2A.X and depletion of survivin-activated ubiquitination of pro-PARP, caspase9, and caspase3. Notably, live cell imaging using confocal microscopy found that BK002 effectively increased DNA-binding red fluorescent intensity in PC3 and DU145 cells. Also, BK002 increased the anti-proliferative effect with activation of the C/EBP homologous protein (CHOP) and significantly attenuated PI3K/AKT expression. Notably, BK002-treated cells increased ROS generation and co-treatment of N-Acetyl-L-cysteine (NAC), an ROS inhibitor, significantly preventing ROS production and cellular cytotoxicity, suggesting that ROS production is essential for initiating apoptosis in PC3 and DU145 cells. In addition, we found that BK002 significantly enhanced miR-192-5p expression, and co-treatment with BK002 and miR-192-5p inhibitor significantly reduced miR-192-5p expression and cellular viability in PC3 and DU145 cells, indicating modulation of miR-192-5p mediated apoptosis. Finally, we found that BK002-mediated CHOP upregulation and PI3K downregulation were significantly reduced and restrained by miR-192-5p inhibitor respectively, suggesting that the anti-cancer effect of BK002 is associated with the miR-192-5p/PI3K/CHOP pathway. Therefore, our study reveals that a combination of AJN and MFR might be more effective than single treatment against apoptotic activities of both CRPC cells and prostate cancer cells.