Anti-Cancer, Anti-Oxidant and Anti-Inflammatory Effects of Herbacetin and Its Molecular Mechanisms

Rhodiola rosea,a perennial herb of the genus Rhodiola in the Crassulaceae family,is commonly used to treat depression,fatigue,cancer and cardiovascular diseases.Herbacetin is a natural flavonol compound extracted from R.rosea plant,with many pharmacological effects such as anti-cancer effect,anti-oxidant effect and anti-inflammatory effect.In this paper,the pharmacological effects and molecular mechanisms of herbacetin were summarized by consulting domestic and foreign literature,in order to provide a theoretical basis for the development and utilization of herbacetin.

Anti-Cancer Agents Associated Diarrhea:Current Status and Prospects

Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.

Regulation of multidrug resistance by microRNAs in anti-cancer therapy

Multidrug resistance(MDR) remains a major clinical obstacle to successful cancer treatment.Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood.Micro RNAs(mi RNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression.Accumulating evidence shows that mi RNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of mi RNAs in regulating MDR in cancer treatment.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Anti-inflammatory and anti-cancer potential of pterostilbene:A review

Pterostilbene is a natural compound that can be found in various food plants such as blueberries,grapes,and peanuts.It has also been reported to be extracted from Pterocarpus indicus,a tree species native to India and Southeast Asia.Pterostilbene exhibits various pharmacological activities such as antioxidants,anti-proliferation,anti-microbial,and anti-inflammatory activities with favorable pharmacokinetic properties,such as high oral bioavailability and longer half-life.The anti-inflammatory effect of pterostilbene has been reported to contribute to its therapeutic effects in many chronic inflammatory diseases.Besides,pterostilbene has anti-cancer activity on various types of cancers due to its ability to induce cell cycle arrest and apoptosis.Hence,in this review,we discuss the anti-inflammatory and anti-cancer activities of pterostilbene in preclinical studies.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation

BACKGROUND At present,colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively.The adverse effects(AEs)of chemotherapy usually interrupt the treatment of chemotherapy.Traditional Chinese medicine(TCM)has demonstrated great potential in improving patients'clinical symptoms,regulating the immune function,improving the life quality,and reducing the AEs of chemotherapy.AIM To observe the clinical efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation.METHODS Data from patients diagnosed with colorectal cancer between January 2019 and February 2021 were collected from Liaoning Cancer Hospital and Institute and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine.Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin(CAPOX)after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group.The experimental group was given Yiqi Jianpi anti-cancer prescription combined with the CAPOX regimen,while the control group was given the CAPOX regimen alone.After six cycles of chemotherapy,the scores of TCM symptoms,Karnofsky performance scale(KPS)score,levels of T-cell subsets,and AEs after chemo therapy of the two groups were compared.RESULTS A total of 70 patients were randomly divided into either an experimental group(n=35,no dropout)or a control group(n=33,with 2 dropouts).Compared with the control group,the experimental group improved significantly(P<0.05)in scores of TCM symptoms,KPS score,levels of T-cell subsets,and AEs of chemotherapy.CONCLUSION Yiqi Jianpi anti-cancer prescription can effectively improve spleen deficiency,regulate the immune function,and alleviate the AEs of chemotherapy,so as to improve the life quality of patients with good therapeutic effects and application prospect in clinical practice.

HIF-1 inhibitors as anti-cancer therapy

Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.The transcription factor HIF-1 mediates cellular response to hypoxia by promoting processes,such as glycolysis and angiogenesis.Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance.Therefore,HIF-1 is a viable target for cancer therapy.This review summarizes agents that have been described in the literature as HIF-1 inhibitors.The majority of these compounds are indirect inhibitors of HIF-1.

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-Ⅱ Photo-Immunotherapy of Metastatic Tumor

Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Effects of hormone replacement therapy on mood and sleep quality in menopausal women

BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.

Exploring the anti-cancer effect of taraxasterol using network pharmacology, molecular docking and in vitro experimental validation

Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.