Advancements in AI Research for Digestive System Diseases

With the “boom” of AI, researchers have made significant progress in assisting clinical disease diagnosis, prediction, and treatment. This article provides an overview of models built using both traditional machine learning methods and deep learning methods, as well as research progress on robotics in digestive system diseases, aiming to provide references for further studies. An application has been developed by domestic and foreign scholars that allows users to upload images of stool samples, which are then analyzed using big data to provide a score for bowel preparation, thereby improving the quality of bowel preparation. In some gastrointestinal diseases, such as Hp infection, Barrett’s esophagus and esophageal cancer, chronic atrophic gastritis and gastric cancer, IBD, etc., artificial intelligence possesses diagnostic capabilities comparable to those of professional endoscopists, and some applications can achieve real-time diagnosis. In the field of liver, gallbladder, and pancreatic diseases, artificial intelligence can assist in preoperative diagnosis using imaging or pathology, and robotic remote operations can be performed during surgery, predicting postoperative risk levels, and more. Different scholars have compared and analyzed various algorithm networks for different diseases to find the best-performing models. On this basis, methods such as the MCA attention mechanism, feature selection, gradient descent, and ensemble models can be introduced to further improve the diagnostic performance of the models. In the future, AI can not only help patients self-manage single or multiple diseases, monitor and manage their own diseases in a standardized and reasonable manner, but also predict and treat digestive system diseases at the genetic level.

Progress in the Study of Inflammatory Bowel Disease Patients with Primary Non-Responsiveness

Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.

Progress in the Study of Laboratory Indicators Related to Acute Pancreatitis

Acute pancreatitis (AP) is one of the more common gastrointestinal diseases in clinics and is characterized by rapid progression, many complications, and high mortality. When it develops into severe pancreatitis, its prognosis is poor. Therefore, early assessment of the degree of inflammatory response plays a crucial role in the treatment plan and prognosis of patients. More and more studies have shown that the levels of D-dimer (D-D), angiotensin-2 (Ang-2), phosphate, heparin-binding protein (HBP), retinol-binding protein-4 (RBP4), and osteoblastic protein (OPN) are closely related to the severity of acute pan-creatitis and can be used as effective indicators for early assessment of AP. In this paper, the research progress of the above indicators in assessing the severity of AP is summarized.

Research Progress of Intestinal Flora in Colorectal Cancer

Colorectal cancer, as a common malignant tumor, has been increasing in incidence year by year and has become one of the leading causes of death worldwide. Meanwhile, researchers have found a close relationship between dysbiosis of the gut microbiota and colorectal cancer, which has further triggered indepth exploration of the role of gut microbiota in the pathogenesis, diagnosis, and treatment of colorectal cancer. Studies have shown that there are specific microbial changes in colorectal cancer tissues, including enrichment or depletion of certain bacterial species, which may be associated with tumor growth, invasion, and metastasis. Additionally, gut microbiota has been found to be closely linked to tumor microenvironment, tumor immune response, chemotherapy drug metabolism, and other factors. In this context, it is imperative to study the gut microbiota in colorectal cancer. A comprehensive understanding of the interaction between gut microbiota and colorectal cancer is not only helpful in revealing novel mechanisms of colorectal cancer development, but also holds promise in providing new strategies and targets for early diagnosis, individualized treatment, and prevention of colorectal cancer. This review aims to thoroughly discuss the research progress of gut microbiota in colorectal cancer, including its compositional characteristics, its role in the occurrence and development of colorectal cancer, and its potential clinical applications. The goal is to provide references and insights for further research in this field.

Progress in the Study of the Hepatoprotective Effect of SGLT2i on NAFLD Patients with T2DM

In recent years, the progress of NAFLD has become an important health problem, and the prevention or delay of progress in NAFLD is a major key point. Whether or not to combine T2MD, people are interested in the mechanisms and efficacy of SGLT2i for NAFLD. In this review, we summarized the current clinical research on SGLT2i for the combination of T2MD’s NAFLD patients, and the latest evidence of external or animal experiments. These evidences will help us to more accurately understand the protective effects of SGLT2i in NAFLD. Lifestyle changes are still essential to prevent and treat NAFLD, and for all kinds of drugs that treat NAFLD in clinical trials, SGLT2i may be one of the promising treatments.

Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia

AIM: To investigate the efficacy and safety of n-3 polyunsaturated fatty acids (PUFA) from seal oils for patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. METHODS: One hundred and forty-four patients with NAFLD associated with hyperlipidemia were included in the 24-wk, randomized, controlled trial. The patients were randomized into two groups. Group A (n = 72) received recommended diet and 2 g n-3 PUFA from seal oils, three times a day. Group B (n = 72) received recommended diet and 2 g placebo, three times a day. Primary endpoints were fatty liver assessed by symptom scores, liver alanine aminotransferase (ALT) and serum lipid levels after 8, 12, 16, and 24 wk. Hepatic fat inf iltration was detected by ultrasonography at weeks 12 and 24 after treatment. RESULTS: A total of 134 patients (66 in group A, 68 in group B) were included in the study except for 10 patients who were excluded from the study. After 24 wk of treatment, no change was observed in body weight, fasting blood glucose (FBG), renal function and blood cells of these patients. Total symptom scores, ALT and triglyceride (TG) levels decreased more significantly in group A than in group B (P < 0.05). As expected, there was a tendency toward improvement in aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), and total cholesterol (TCHO) and high- density lipoprotein (HDL) cholesterol levels (P < 0.05) after administration in the two groups. However, no significant differences were found between the two groups. The values of low-density lipoprotein (LDL) were significantly improved in group A (P < 0.05), but no significant change was found in group B at different time points and after a 24-wk treatment. After treatment, complete fatty liver regression was observed in 19.70% (13/66) of the patients, and an overall reduction was found in 53.03% (35/66) of the patients in group A. In contrast, in group B, only f ive patients (7.35%, 5/68) achieved complete fatty liver regression (P = 0.04), whereas 24 patients (35.29%, 24/68) had a certain improvement in fatty liver (P = 0.04). No serious adverse events occurred in all the patients who completed the treatment. CONCLUSION: Our results indicate that n-3 PUFA from seal oils is safe and effi cacious for patients with NAFLD associated with hyperlipidemia and can improve their total symptom scores, ALT, serum lipid levels and normalization of ultrasonographic evidence. Further study is needed to confi rm these results.

Clostridium difficile infection and inflammatory bowel disease:Understanding the evolving relationship

Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.

Liver transplantation for nonalcoholic fatty liver disease:New challenges and new opportunities

Nonalcoholic fatty liver disease(NAFLD)is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world.Development of graft steatosis is a significant problem during the posttransplant course,which may happen as a recurrence of pre-existing disease or de novo NAFLD.There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome,immune-suppressive medications,genetics and others.There are few studies that assessed the effects of NAFLD on graft and patient survival;most of them were limited by the duration of follow up or by the number of patients.With this review article we will try to shed light on post-liver transplantation NAFLD,significance of the disease,how it develops,risk factors,clinical course and treatment options.

Recent advances in dietary supplementation, in treating non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is currently known as the most common liver problem, characterized by excessive lipid accumulation in hepatocytes,which may progress to other liver diseases such as nonalcoholic steatohepatitis, hepatic tissue fibrosis, livercirrhosis, and failure or hepatocellular carcinoma. Since NAFLD is positively associated with the development of obesity, insulin resistance, and ultimately type 2 diabetes mellitus, it is often regarded as the hepatic manifestation of the metabolic syndrome. No pharmacologic treatment has yet been proven for this disease. For most patients with presumed or confirmed NAFLD, the only proven strategy is to offer lifestyle advice that can lead to sustained weight loss. Since insulin resistance, oxidative stress, inflammation, and necro-apoptosis are involved in NAFLD pathogenesis, it seems that every potential therapeutic agent should target one or some of these pathologic events. There are many well known anti-oxidants, anti-inflammatory, and insulin sensitizer dietary supplements which have shown beneficial effects on NAFLD improvement in animal and human studies. The purpose of this review is to explore the existing evidences on dietary supplements considered to have hepatoprotective properties, and to present some proposed mechanisms by which they may protect against NAFLD.

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease

AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm nonalcoholic liver disease(NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score(NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic(ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis,lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08(95%CI: 1.03-1.14), 1.04(95%CI: 1.008-1.07), 1.04(95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4(95%CI: 1.09-1.8), 1.07(95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06(95%CI: 1.002-1.12), 19.86(95%CI: 2.79-141.19), 560.72(95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05(95%CI: 1.01-1.1), 1.13(95%CI: 1.04-1.22), P < 0.05]. CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.

Reciprocal impact of host factors and Helicobacter pylori genotypes on gastric diseases

AIM: To assess the impact of Helicobacter pylori(H. pylori) genotypes and patient age and sex on the development of gastric diseases.METHODS: H. pylori-infected patients(n = 233) referred to the endoscopy unit at Tehran University of Medical Sciences(Tehran,Iran) were diagnosed with chronic gastritis(CG),gastric ulcer(GU),or duodenal ulcer(DU). Brucella blood agar was used for biopsy cultures and H. pylori isolation under microaerobic conditions. H. pylori isolates were confirmed with biochemical tests and through amplification of the 16 S r RNA gene. DNA was extracted from fresh cultures of the H. pylori isolates and used for amplification of vac A alleles and the cag A gene. Statistical analysis was performed to determine the association between H. pylori genotypes,age(< 40 years vs > 40 years) and sex of the patient,and gastric diseases.RESULTS: CG was the most prevalent gastric disease(113/233; 48.5%),compared to GU(64/233; 27.5%)and DU(56/233; 24%). More patients were male,and gastric diseases were more frequent in patients > 40 years(P < 0.05). The percentage of CG and GU patients that were male and female did not show a significant difference; however DU was more common in males(P < 0.05). Interestingly,a diagnosis of CG in patients > 40 years was more common in females(18.5%) than males(11.6%)(P = 0.05),whereas a diagnosis of GU or DU in patients > 40 years was more frequent in males(14.6% vs 10.7% and 12.4% vs 4.3%,respectively). Overall,genotyping of the H. pylori isolates revealed that the vac A s1(82%),vac A m2(70%),and cag A+(72.5%) alleles were more frequent than vac A s2(18%),vac A m1(29.2%),and cag A-(all P < 0.05). The vac A s1m2 cag A+ genotype was the most prevalent within the three disease groups. vac A s1m2 frequency was 56.2% with a similar occurrence in all diagnoses,while vac A s1m1 appeared more often in DU patients(33.9%). A genotype of vac A s2m2 occurred in 15% of isolates and was more common in CG patients(21.2%); vac A s2m1 was the least common genotype(3%). The vac A s1 allele was found to be a risk factor for DU,vac A s2 for CG,and vac A s1 and vac A s2 for GU(all P < 0.05). The vac A s2m2 genotype was associated with the development of CG and GU compared to DU(P < 0.05). No correlation was found between vac A m or cag A and gastric diseases.CONCLUSION: The outcome of H. pylori infection is the result of interaction between bacterial genotypes and the age and sex of infected individuals.

Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease

AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.

Contemporary surgical management of rectovaginal fistula in Crohn's disease

Rectovaginal fistula is a disastrous complication of Crohn's disease(CD) that is exceedingly difficult to treat. It is a disabling condition that negatively impacts a women's quality of life. Successful management is possible only after accurate and complete assessment of the entire gastrointestinal tract has been performed. Current treatment algorithms range from observation to medical management to the need for surgical intervention. A wide variety of success rates have been reported for all management options. The choice of surgical repair methods depends on various fistula and patient characteristics. Before treatment is undertaken, establishing reasonable goals and expectations of therapy is essential for both the patient and surgeon. This article aims to highlight the various surgical techniques and their outcomes for repair of CD associated rectovaginal fistula.

Egg consumption and risk of non-alcoholic fatty liver disease

AIM To evaluate the association between egg consumption and risk of non-alcoholic fatty liver disease(NAFLD) development.METHODS This case-control study was conducted on individuals who were referred to two hepatology clinics in Tehran, Iran in 2015. The study included 169 patients with NAFLD and 782 controls. Egg consumption was estimated using a validated food frequency questionnaire. The participants were categorized according to the frequency of their egg consumption during the previous year: Less than two eggs per week, two to three eggs per week, and four or more eggs per week.RESULTS In the crude model, participants who consumed 2 to 3 eggs per week, were 3.56 times more likely to have NAFLD in comparison to those who consumed less than 2 eggs per week(OR: 3.56; 95%CI: 2.35-5.31). Adjustment for known risk factors of NAFLD strengthenedthis significant association so that individuals have consumed two to three eggs per week had 3.71 times higher risk of NAFLD than those who have eaten less than two eggs per week(OR: 3.71; 95%CI: 1.91, 7.75). CONCLUSION Our data indicate that higher egg consumption in common amount of usage is associated with higher risk of NAFLD.

First United Arab Emirates consensus on diagnosis and management of inflammatory bowel diseases:A 2020 Delphi consensus

Ulcerative colitis and Crohn’s disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract.The incidence and prevalence are on the rise worldwide,and the heterogeneity between patients and within individuals over time is striking.The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients.This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence-and expert opinion-based recommendations.Comprehensive up-to-date guidance is provided regarding diagnosis,evaluation of disease severity,appropriate and timely use of different investigations,choice of appropriate therapy for induction and remission phase according to disease severity,and management of main complications.

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Impact of Lamivudine plus Adefovir therapy in chronic hepatitis B Iranian patients, resistant to Lamivudine treatment alone, on disease inhibition: A pilot study

AIM: To evaluate the impact of combination therapy with Lamivudine and Adefovir for treatment of chronic hepatitis B in Lamivudine-resistant patients. METHODS: Among the 110 adult chronic hepatitis B Iranian patients whom were treated with Lamivudine, for 36 months, nineteen patients (17%) with no any biochemical and viral responses to Lamivudine alone, were selected and enrolled in the study. Due to resistancy, Adefovir was added to Lamivudine, and continued for 30 months. We measured HBV_DNA viral load and serum AST, ALT in 0, 12, 24, 30 and 0, 6, 12, 18, 24, 30 months, respectively. RESULTS: Between biochemical and viral characteristics, Repeated Measure analysis identified just biochemical markers— Aspartate Aminotransferase level (AST) (P = 0.002) and Alanine Aminotransferase level (ALT) (P = 0.007) —as predictors of response to treatment, while, viral marker—HBV DNA load—was not statistically significant (P = 0.128). CONCLUSIONS: Treatment for a long time, such as 21.5 ± 8.8 months, with Lami- vudine and Adefovir, can cause liver enzymes including AST and ALT, decreasing and being normal. But, this finding is not indicative, for HBV-DNA viral load.

The Mechanism and Research Progress of Ferroptosis in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC), as the main histological type of esophageal cancer (EC), has the characteristics of high malignant degree, high mortality and tendency to lymph node metastasis. Despite the combination of surgery and chemoradiotherapy, ECSS has a poor prognosis. Ferroptosis is a newly discovered iron-dependent programmed cell death pattern characterized by the accumulation of lipid peroxidation and characteristic morphological changes of mitochondria. It regulates the growth and invasion of cancer cells in various tumors such as gastric cancer and pancreatic cancer. In this article, we mainly introduce the ferroptosis regulatory mechanism in ESCC, hoping to provide a new direction and ideas for the treatment of ECSS.

Organized physical activity and sedentary behaviors in children and adolescents with autism spectrum disorder,cerebral palsy,and intellectual disability

BACKGROUND There is little data on physical activity(PA),organized PA(OPA),and sedentary behaviors in autism spectrum disorders(ASD)and other neurodevelopmental disorders in developing countries.AIM To examine OPA,non-OPA,and sedentary behaviors and their associated factors in children and adolescents with ASD,cerebral palsy(CP),and intellectual disability(ID).METHODS A total of 1020 children and adolescents with ASD,CP,and ID were assessed regarding the child and family information as well as the Children’s Leisure Activities Study Survey.RESULTS The results showed that the OPA level was significantly lower than non-OPA in all groups.Furthermore,the OPA level was significantly lower in the CP group compared to ASD and ID groups(P<0.001).Also,moderate(P<0.001),vigorous(P<0.05),and total(P<0.001)physical activity levels were significantly different between all three groups,with the values being higher in the ASD group compared to the other two.The mean of the total sedentary behavior duration in the ASD group(1819.4 min/week,SD:1680)was significantly lower than in the CP group(2687 min/week,SD:2673)(P=0.007)but not ID group(2176 min/week,SD:2168.9)(P=0.525).CONCLUSION Our findings remark on the participation rate of PA,OPA,and sedentary behaviors of children and adolescents with ASD,CP,and ID in a developing country.In contrast,the need for developing standards of PA/OPA participation in neurodevelopmental disorders is discussed.

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease progression.As an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease development.Extensive research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue concentration.This has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer progression.Zinc transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc intake.Additionally,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on cancer.We also compile a summary of clinical trials involving zinc ions.Given the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.