Natural Compounds Targeting the Autophagy Pathway in the Treatment of Colorectal Cancer.

Autophagy is a highly conserved intracellular degradation pathway by which misfolded proteins or damaged organelles are delivered in a double-membrane vacuolar vesicle and finally degraded by lysosomes. The risk of colorectal cancer (CRC) is high, and there is growing evidence that autophagy plays a critical role in regulating the initiation and metastasis of CRC; however, whether autophagy promotes or suppresses tumor progression is still controversial. Many natural compounds have been reported to exert anticancer effects or enhance current clinical therapies by modulating autophagy. Here, we discuss recent advancements in the molecular mechanisms of autophagy in regulating CRC. We also highlight the research on natural compounds that are particularly promising autophagy modulators for CRC treatment with clinical evidence. Overall, this review illustrates the importance of autophagy in CRC and provides perspectives for these natural autophagy regulators as new therapeutic candidates for CRC drug development.

Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells.

Our previous study found that the combination of halofuginone (HF) and artemisinin (ATS) synergistically arrest colorectal cancer (CRC) cells at the G1/G0 phase of the cell cycle; however, it remains unclear whether HF-ATS induces cell death. Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells. Specifically, both in vitro and in vivo experiments showed that HF or HF-ATS induces apoptosis via activation of caspase-9 and caspase-8 while only caspase-9 is involved in ATS-induced apoptosis. Furthermore, we found HF or HF-ATS induces autophagy; ATS can't induce autophagy until caspase-9 is blocked. Further analyzing the crosstalk between autophagic and caspase activation in CRC cells, we found autophagy is essential for activation of caspase-8, and ATS switches to activate capase-8 via induction of autophagy when caspase-9 is inhibited. When apoptosis is totally blocked, HF-ATS switches to induce autophagic cell death. This scenario was then confirmed in studies of chemoresistance CRC cells with defective apoptosis. Our results indicate that HF-ATS induces cell death via interaction between apoptosis and autophagy in CRC cells. These results highlight the value of continued investigation into the potential use of this combination in cancer therapy.

WHO Trial Registration Data Set (TRDS) extension for traditional Chinese medicine 2020: recommendations, explanation, and elaboration.

BACKGROUND: Although the WHO Trial Registration Data Set (TRDS) has been published for many years, the quality of clinical trial registrations with traditional Chinese medicine (TCM) is still not satisfactory, especially about the inadequate reporting on TCM interventions. The development of the WHO TRDS for TCM Extension 2020 (WHO TRDS-TCM 2020) aims to address this inadequacy. METHODS: A group of clinical experts, methodologists, epidemiologists, and editors has developed this WHO TRDS-TCM 2020 through a comprehensive process, including the baseline survey, draft of the initial items, three-round of Delphi survey, solicitation of comments, revision, and finalization. RESULTS: The WHO TRDS-TCM 2020 statement extends the latest version (V.1.3.1) of TRDS published in November 2017. The checklist includes 11 extended items (including subitems), namely Source(s) of Monetary or Material Support (Item 4), Scientific Title (Item 10a and 10b), Countries of Recruitment (Item 11), Health Condition(s) or Problem(s) Studied (Item 12), Intervention(s) (Item 13a, 13b and 13c), Key Inclusion and Exclusion Criteria (Item 14), Primary and Key Secondary Outcomes (Item 19 to 20), and Lay Summary (Item B1). For Item 13 (Interventions), three common TCM interventions--i.e., Chinese herbal medicine formulas, acupuncture and moxibustion-are elaborated. CONCLUSIONS: The group hopes that the WHO TRDS-TCM 2020 can improve the reporting quality and transparency of TCM trial registrations, assist registries in assessing the registration quality of TCM trials, and help readers understand TCM trial design.

A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China.

OBJECTIVE: Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients. METHODS: A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process. RESULTS: We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs. CONCLUSION: This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).

PRISMA extension for moxibustion 2020: recommendations, explanation, and elaboration.

BACKGROUND: Moxibustion is a common intervention of Chinese medicine (CM). Systematic reviews (SRs) on moxibustion are increasing. Although the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement provides guidelines for SRs, the quality of moxibustion-related SRs is still not satisfactory. In particular, descriptions of the interventions and the rationale for using moxibustion are insufficient. To address these inadequacies, the working group developed this PRISMA extension for reporting SRs of moxibustion (PRISMA-M 2020). METHODS: A group of CM clinical professionals, methodologists of SRs, reporting guideline developers, and journal editors developed this PRISMA-M 2020 through a comprehensive process that includes registration, literature review, consensus meetings, Delphi exercises for soliciting comments, and revision, resulting in this final draft. RESULTS: Seven of the 27 PRISMA checklist items, namely title (1), rationale (3), eligibility criteria (6), data item (11), additional analyses (16), study characteristics (18), and additional analysis (23), were extended, with specific reference to the application of moxibustion. Illustrative examples and explanations for each item are provided. CONCLUSION: The PRISMA-M 2020 will help improve the reporting quality of SRs with moxibustion. SYSTEMATIC REVIEW REGISTRATION: We have registered it on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network, particularly under the item of PRISMA-TCM: http://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-systematic-reviews/#65 .

An oligosaccharide-marker approach to quantify specific polysaccharides in herbal formula by LC-qTOF-MS: Danggui Buxue Tang, a case study.

Polysaccharides have broad bioactivities and are major components of water decoction of herb formulae. However, the quality control of polysaccharides remains a challenge. Oligosaccharide-fragment approach has been considered in elucidating chemical structures of polysaccharides, but never been used for quantitation. Using reference chemicals and a real sample Danggui Buxue Tang (DBT) in this study, an oligosaccharide-marker approach was established to quantify specific polysaccharides. Firstly, linear relationships between parent polysaccharides and hydrolysis-produced daughter oligosaccharides were verified using reference polysaccharides. Then in case of DBT, two fluorescence-labeled oligosaccharides with high specificity to individual parent polysaccharides were selected as markers. They were easily isolated and identified. Their potential in quantification of parent polysaccharides were satisfactorily validated in terms of linearity (r≥0.99), repeatability (RSD ≤ 8.4 %), and spike recovery (≥80 %). This method could be a promising approach for quality assessment of polysaccharides in herbal formulae.

Standard Protocol Items for Clinical Trials with Traditional Chinese Medicine 2018: Recommendations, Explanation and Elaboration (SPIRIT-TCM Extension 2018).

Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.