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.

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.

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.

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.

Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects

Photodynamic therapy(PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer(PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be-sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment.

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.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Real-world evidence on the efficacy and safety of vonoprazanamoxicillin dual therapy for Helicobacter pylori treatment in elderly patients

BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly patients.AIM To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for H.pylori in elderly patients.METHODS As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for H.pylori eradication in the Department of Gastroenterology at Peking University First Hospital between June 2020 and January 2024.H.pylori status was evaluated by^(13)C-urease breath test 6 weeks after treatment.All adverse events(AEs)during treatment were recorded.RESULTS In total,401 cases were screened.Twenty-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take medication.The total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue treatment.H.pylori was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment group.The overall incidence of AEs was 9.5%for both groups.Specifically,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment group.Five patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE occurred.CONCLUSION The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Current status of drug therapy for chronic hepatitis B

In this editorial,we comment on the article by Meng et al.Chronic hepatitis B(CHB)is a significant global health problem,particularly in developing countries.Hepatitis B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.Prevention and treatment of HBV are key measures to reduce complications.At present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a challenge.Anti-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’compliance.We will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma

In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.

Summary of the current guidelines for managing iatrogenic colorectal perforations and the evolving role of endoluminal vacuum therapy

Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal diseases.During the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic colonoscopies.The recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased risk.The incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe cases.Recently,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case reports.This editorial provides an overview of the current guidelines for the management of iatrogenic colorectal perforations.These insights are from the perspectives of endoscopists and gastroenterologists.We also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency Surgery.We also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Current perspectives and the future of disease-modifying therapies in type 1 diabetes

Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.

Root canal therapy combined with endoscopic sinus surgery for odontogenic sinusitis:Efficacy comparison in a cohort study

BACKGROUND Odontogenic maxillary sinusitis,often triggered by dental issues like periapical periodontitis,significantly contributes to chronic sinusitis,mainly affecting adults around 50 years old,emphasizing the need for a multidisciplinary diagnostic and treatment approach.AIM To investigate the therapeutic effect and clinical value of root canal therapy combined with nasal endoscopic surgery compared with simple root canal the-rapy in the treatment of severe odontogenic maxillary sinusitis caused by peria-pical periodontitis.METHODS The clinical data,diagnosis,and treatment of 200 patients with severe odonto-genic maxillary sinusitis caused by periapical periodontitis from October 2020 to October 2021 were analyzed retrospectively.Among them,63 patients were treated with simple root canal therapy as the control group,and 137 patients were treated with root canal therapy combined with nasal endoscopic surgery as the observation group.The therapeutic effect,Lund-Kennedy endoscopic score,paranasal sinus Lund-Mackay score,complication rate,recurrence rate,and patient satisfaction were compared between the two groups.RESULTS First,we compared the effective rates:23 cases were cured,22 were improved,and 8 were ineffective in the control group,yielding a total effective rate of 84.90%.Meanwhile,97 cases were cured,34 improved,and 6 were ineffective in the observation group,resulting in a total effective rate of 95.62%.The observation group had a higher total effective rate compared with the control group(P<0.05).Second,we compared the Lund–Kennedy endoscopic score.Before treatment,no significant difference(P>0.05)was observed in this score between the two groups.After treatment,the Lund–Kennedy endoscopic score decreased in both groups.The Lund–Kennedy endoscopic score of the observation group at 3 and 6 mo after treatment was lower compared to that of the control group(P<0.05).Third,we compared the Lund–Mackay score of paranasal sinuses.Before treatment,there was no significant difference in this score between the two groups(P>0.05).After treatment,the Lund–Mackay scores of paranasal sinuses decreased in both groups.The Lund–Mackay scores of paranasal sinuses in the observation group at 3 and 6 mo after treatment were lower compared to those of the control group(P<0.05).Fourth,we compared the incidence and recurrence rate of complications.Three months after treatment,no significant difference was found in the incidence and recurrence rate of complications between the observation group(6.56%)and the control group(9.52%)(P>0.05).However,6 mo after treatment,the incidence and recurrence rate of complications in the observation group(2.91%)was significantly higher compared to that of the control group(12.69%)(P<0.05).Fifth,we compared patient satisfaction.Six months after treatment,the patient satisfaction of the observation group(93.43%)was significantly better than that of the control group(84.12%)(P<0.05).CONCLUSION Root canal therapy combined with nasal endoscopic surgery has a good therapeutic effect on severe odontogenic maxillary sinusitis caused by periapical periodontitis,and it can reduce the injury of maxillary sinus mucosa and bone,and significantly reduce the incidence of complications and recurrence rate.Meanwhile,it has high patient satisfaction and remarkable therapeutic effect,which is suggested to be popularized and applied in clinic.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

A Self-assembled Nanomicelle for Realizing Tumor Photodynamic Therapy via Increasing Drug Accumulation and Prolonging Retention Time

A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.

Multimodal treatment combining neoadjuvant therapy,laparoscopic subtotal distal pancreatectomy and adjuvant therapy for pancreatic neck-body cancer:Case series

BACKGROUND Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels,making its radical resection challenging.Multimodal treatment strategies,including neoadjuvant therapy,surgery,and postoperative adjuvant therapy,are contributing to a paradigm shift in the treatment of pancreatic cancer.This strategy is also promising in the treatment of pancreatic neckbody cancer.AIM To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer.METHODS From January 2019 to December 2021,we reviewed the demographic characteristics,neoadjuvant and adjuvant treatment data,intraoperative and postoperative variables,and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital.This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria.RESULTS A total of 11 patients with pancreatic neck-body cancer were included in this study,of whom 6 patients were borderline resectable and 5 were locally advanced.Through multidisciplinary team discussion,all patients received neoadjuvant therapy,of whom 8(73%)patients achieved a partial response and 3 patients maintained stable disease.After multidisciplinary team reassessment,all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection.Postoperatively,two patients(18%)developed ascites,and two patients(18%)developed pancreatic fistulae.The median length of stay of the patients was 11 days(range:10-15 days).All patients received postoperative adjuvant therapy.During the follow-up,three patients experienced tumor recurrence,with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months.CONCLUSION A multimodal treatment strategy combining neoadjuvant therapy,laparoscopic subtotal distal pancreatectomy,and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.

New perspectives and prospects for the next generation of combination therapy in inflammatory bowel disease

This article comments on the letter by Lowell et al,which addresses the next generation of combination therapy for inflammatory bowel disease(IBD).As the understanding of the pathogenesis of IBD continues to improve,treatment strategies are evolving rapidly.The letter examines the current status and future directions of combination therapy for IBD,focusing on approaches that combine biologics with immunomodulators and the emerging dual-biologic therapy(DBT).The traditional combination of biologics and immunomodulators has demonstra-ted preliminary efficacy by enhancing the effects of biologics through immunomo-dulation.However,concerns regarding long-term safety warrant careful evalua-tion.Recent trials,including DUET-Crohn's disease and DUET-ulcerative colitis,have shown promising potential for the broader adoption of DBT.Nevertheless,comprehensive data on efficacy and safety,as well as the effective integration of supportive treatments,remain essential to establish new paradigms for the next generation of IBD care.

Genetic factors that predict response and failure of biologic therapy in inflammatory bowel disease

Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.