Pharmacological effects of ginseng and ginsenosides on intestinal inflammation and the immune system.

Intestinal inflammatory imbalance and immune dysfunction may lead to a spectrum of intestinal diseases, such as inflammatory bowel disease (IBD) and gastrointestinal tumors. As the king of herbs, ginseng has exerted a wide range of pharmacological effects in various diseases. Especially, it has been shown that ginseng and ginsenosides have strong immunomodulatory and anti-inflammatory abilities in intestinal system. In this review, we summarized how ginseng and various extracts influence intestinal inflammation and immune function, including regulating the immune balance, modulating the expression of inflammatory mediators and cytokines, promoting intestinal mucosal wound healing, preventing colitis-associated colorectal cancer, recovering gut microbiota and metabolism imbalance, alleviating antibiotic-induced diarrhea, and relieving the symptoms of irritable bowel syndrome. In addition, the specific experimental methods and key control mechanisms are also briefly described.

Moringin alleviates DSS-induced ulcerative colitis in mice by regulating Nrf2/NF-κB pathway and PI3K/AKT/mTOR pathway.

Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD), which is a chronic and immune-mediated inflammatory disease. Moringin (MOR) is an isothiocyanate isolated from Moringa oleifera Lam., and has been recognized as a promising potent drug for inflammatory diseases and antibacterial infections. The present study investigated the role of moringin in dextran sulfate sodium (DSS)-induced UC mice. Mouse colitis was induced by adding DSS to the drinking water for seven consecutive days. Our experimental results showed that MOR relieves DSS-induced UC in mice by increasing body weight and colonic length, and reducing the disease activity index and histological injury. Mechanistically, MOR improves intestinal barrier function by increasing the expression of tight junction proteins (TJPs) and enhancing the secretion of mucin in DSS-induced mice. MOR inhibits inflammatory response and intestinal damage by regulating Nrf2/NF-κB signaling pathway and modulating the PI3K/AKT/mTOR pathway. Furthermore, in Nrf2 knockout (Nrf2-/-) mice, the protective effects of MOR on DSS-induced UC were abolished. Meanwhile, treatment with MOR reduced inflammation and cell damage via regulating Nrf2/NF-κB pathway in a lipopolysaccharide (LPS)-induced inflammation model of Caco-2 cells. In contrast, ML385, an Nrf2 inhibitor, might eliminate the protection provided by MOR. Notably, treatment with MOR significantly up-regulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), suggesting that MOR may be a potential PPAR-γ activator. In conclusion, MOR exerts protective effect in UC by improving intestinal barrier function, regulating Nrf2/NF-κB and PI3K/AKT/mTOR signaling pathways, and another effect associated with the regulation of PPAR-γ expression.

Biochanin a ameliorates DSS-induced ulcerative colitis by improving colonic barrier function and protects against the development of spontaneous colitis in the Muc2 deficient mice.

There is an increasing appreciation that colonic barrier function is closely related to the development and progression of colitis. The mucus layer is a crucial component of the colonic barrier, responsible for preventing harmful bacteria from invading the intestinal epithelium and causing inflammation. Furthermore, a defective mucus barrier is also a significant characteristic of ulcerative colitis (UC). Biochanin A (BCA), an isoflavonoid, has garnered increasing interest due to its significant biological activities. However, the impact of BCA on UC has not been reported yet. In this study, we used a dextran sodium sulfate (DSS)-induced ulcerative colitis model and the Muc2 deficient (Muc2-/-) mice spontaneous colitis model to explore the mechanisms of BCA in the treatment of UC. Here, we verified that DSS-induced UC was observably attenuated and spontaneous colitis in Muc2-/- mice was relieved by BCA. Treatment with BCA improved colitis-related symptoms and reduced intestinal permeability by upregulating the levels of goblet cells and tight junction (TJ) proteins. In addition, we confirmed that BCA promotes autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway, thereby alleviating DSS-induced UC. In addition, the administration of BCA was able to reduce apoptosis and promote proliferation by suppressing Cleaved Caspase-3 (Cleaved Cas-3) expression, and increasing PCNA and Ki67 levels. Further research revealed that BCA treatment ameliorated spontaneous colitis and alleviated epithelial damage in Muc2-/- mice by restoring the intestinal barrier and promoting autophagy. Our results demonstrated that BCA alleviated UC by enhancing intestinal barrier function and promoting autophagy. These findings indicate that BCA may be a novel treatment alternative for UC.

Isoliquiritin counteracts cadmium-induced intestinal damage in mice through enhancing intestinal barrier function and inhibiting apoptosis.

Cadmium (Cd), a crucial toxic environmental pollutant, can induce damage to many organs, especially the gastrointestinal tract. Isoliquiritin (ISO), a critical flavonoid glycoside compound isolated from Glycyrrhiza uralensis, has anti-inflammatory, anticancer, antioxidant and other pharmaceutical value. However, the potential roles of ISO in Cd-induced intestinal damage have not been reported yet. This study aimed to research the beneficial effects of ISO on Cd-induced intestinal damage and identify its underlying mechanisms. Our results showed that ISO reduced inflammation by suppressing the production of pro-inflammatory cytokines and the activity of serum Lipopolysaccharide (LPS) in mice with Cd exposure. In terms of mechanism, ISO administration protected the intestinal barrier function through increasing the expression of tight junction proteins and Muc2. Furthermore, ISO could significantly suppress Cd-induced intestinal apoptosis and activation of NLRP3 inflammasome. Interestingly, inhibiting the activation of NLRP3 by nigericin completely blocking the effect of ISO on apoptosis. Most importantly, ISO markedly abrogated Cd-induced cell damage and NLRP3 inflammasome activation in vitro. Taken together, these findings suggest that ISO reduces Cd-induced intestinal damage by increasing the goblet cells, improving intestinal barrier, suppressing NLRP3 inflammasome activation and inhibiting apoptosis, which may offer a novel strategy against the toxic effects of heavy metals.

α-Lipoic acid alleviates dextran sulfate sodium salt-induced ulcerative colitis via modulating the Keap1-Nrf2 signaling pathway and inhibiting ferroptosis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disease with severe diarrhea, fatigue and weight loss. α-Lipoic acid (LA), a well-known antioxidant, is able to scavenge reactive oxygen species (ROS) and maintain a healthy cellular redox state. However, the role of LA in protecting IBD is still unclear. Hence the aim of this research was to investigate the protective effect of LA on dextran sulfate sodium salt-induced ulcerative colitis (UC) and its underlying mechanism. RESULTS: Here, our findings showed that LA significantly alleviated UC symptoms and the overproduction of pro-inflammatory cytokines in UC mice. In addition, LA treatment inhibited intestinal cell apoptosis by regulating the expression levels of p53/caspase-3 pathway-related protein in UC mice. Meanwhile, the inhibitory effects of LA on colonic oxidative stress and ferroptosis were revealed. Our study further demonstrated that LA treatment could regulate the Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Interestingly, we confirmed that LA inhibited ferroptosis by attenuating endoplasmic reticulum stress and suppressing apoptosis in erastin-induced ferroptosis model in vitro. CONCLUSION: Taken together, this study's findings suggest that LA could be considered as a therapeutic agent protecting against IBD. © 2023 Society of Chemical Industry.

The interaction between ginseng and gut microbiota.

The importance of the gut microbiota to human health is attracting increasing attention. It is also involved in ginseng metabolism, mediating the bioactive metabolites of ginsenosides. In response, ginseng, known as the king of herbs, can regulate intestinal flora, including promoting probiotics and restricting the growth of harmful bacteria. Specifically, the interactions between ginseng or ginsenosides and gastrointestinal microbiota are complex. In this review, we summarized the effects of ginseng and ginsenosides on the composition of gut microbiota and discussed the gut microbiota-mediated biotransformation of ginsenosides. In particular, their therapeutic potential and clinical application in related diseases were also summarized.

Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.

Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.

Nuciferine protects against lipopolysaccharide-induced endometritis via inhibiting ferroptosis and modulating AMPKα/mTOR/HIF-1α signaling axis.

Nuciferine (NF) is an alkaloid isolated from Nelumbo nucifera and has been reported to exhibit a wide range of pharmacological effects. However, whether NF treatment exhibits a protective effect in endometritis remains unclear. Here, the protective effects of NF on lipopolysaccharide (LPS)-induced endometritis in mice were investigated in our research. The results showed that NF significantly reversed the uterine histopathological changes, inflammatory factor levels and myeloperoxidase (MPO) activity caused by LPS. Furthermore, we found that NF administration improved the reproductive capacity of mice with endometritis. Mechanistically, the expression of MyD88/nuclear factor-kappa B (NF-κB) and MAPK-related proteins in uterine tissue were decreased by NF treatment. Moreover, we observed the occurrence of ferroptosis in the LPS-induced endometritis mouse model, which was noticeably inhibited by NF treatment. In addition, we showed that NF exhibited anti-endometritis activity by modulating AMPKα/mTOR/HIF1α signaling axis. Finally, the molecular mechanism of the NF anti-inflammatory effect was clarified in mouse endometrial epithelial cells (mEECs). NF inhibited the releases of pro-inflammatory factors in LPS-induced mEECs via inhibiting NF-κB signaling pathway. All these findings suggest that NF may ameliorate LPS-induced endometritis caused by LPS, the mechanism of action is related to the ferroptosis, MyD88/NF-κB, MAPK and AMPKα/mTOR/HIF1α signaling pathway.

Potential role of irisin in digestive system diseases.

Digestive system diseases (DSD) are very complex conditions that severely threaten human health. Therefore, there is an urgent need to develop new pharmacological treatment strategies. Irisin, a myokine discovered in 2012, is produced by fibronectin type III domain-containing protein 5 (FNDC5), which is a transmembrane protein. Irisin is involved in promoting the browning of white adipose tissue, the regulation of energy metabolism, and the improvement of insulin resistance. Irisin is also an essential mediator of the inflammatory response, oxidative stress, and cell apoptosis. Recent studies have proved that irisin concentration is altered in DSD and exerts pivotal effects on the initiation, progression, and prognosis of these diseases through various mechanisms. Therefore, studying the expression and function of irisin may have great significance for the diagnosis and treatment of DSD. Here, we focus on irisin and explore the multiple molecular pathways targeted by irisin therapy. This review indicates that irisin can serve as a diagnostic marker or potential therapeutic agent for DSD. DATA AVAILABILITY: Not applicable.

Polygonati Rhizoma with the homology of medicine and food: A review of ethnopharmacology, botany, phytochemistry, pharmacology and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizoma (PR), which contains rich national cultural connotations, is a traditional Chinese medicine with homology of medicine and food. It has been used for a long time as a tonic in China's multi-ethnic medical system, and is also used to treat diseases such as premature graying hair, deficiency of blood and essence, diabetes, hypertension, etc. Meanwhile, PR is often used as food in China, India, South Korea and other Asian countries, which can satisfy hunger and provide many health benefits. AIM OF THE REVIEW: This paper systematically reviewed the ethnopharmacology, botany, phytochemistry, pharmacology and related applications research of PR, and provided a reference for the comprehensive applications of PR, including basic research, product development and clinical applications. This paper also refined the national application characteristics of PR, such as rich plant resources, special chemical components and anti-hidden hungry, which laid a foundation for its high value and high connotation development in the future. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine. RESULTS: A comprehensive analysis of the above literature confirmed that PR has been used in the ethnic medicine system of Asian countries such as China for thousands of years. In this paper, 12 species including official species that can be used as PR are summarized, which provide rich plant resources for PR. The chemical components in PR are divided into nutritional components and active components. The former not only contains non-starch polysaccharides and fructo-oligosaccharides, which account for about 50% in PR and are recognized as high-quality diet in the world, but also contains inorganic elements and mineral elements. And a total of 199 kinds active ingredients, including saponins, flavonoids, alkaloids, etc., were sorted out by us. The above ingredients make PR have a special property of anti-hidden hunger. Studies have shown that PR has a wide range of pharmacological activities, such as immune regulation, blood glucose regulation, lipid-lowering, antioxidant, anti-tumor, antibacterial, etc. It has been widely used in medicine, food, cosmetics, gardens and other fields. CONCLUSIONS: PR, as a classic medicinal material of the same origin, is widely used in the traditional ethnic medicine system. It contains abundant potential plant resources, chemical components and pharmacological activities. This paper also suggests that PR with high application value in food industry, has the potential to become a high-quality coarse grain. Exploring the way of grain and industrialization of PR is beneficial to fully develop the economic value of PR.

Evaluation of 20(S)-ginsenoside Rg3 loaded hydrogel for the treatment of perianal ulcer in a rat model.

Background: As a kind of common complication of the surgery of perianal diseases, perianal ulcer is known as a nuisance. This study aims to develop a kind of 20(S)-ginsenoside Rg3 (Rg3)-loaded hydrogel to treat perianal ulcers in a rat model. Methods: The copolymers PLGA1600-PEG1000-PLGA1600 were synthesized by ring-opening polymerization process and Rg3-loaded hydrogel was then developed. The perianal ulcer rat model was established to analyze the treatment efficacy of Rg3-loaded hydrogel for ulceration healing for 15 days. The animals were divided into control group, hydrogel group, free Rg3 group, Rg3-loaded hydrogel group, and Lidocaine Gel® group. The residual wound area rate was calculated and the blood concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were recorded. Hematoxylin and eosin (H&E) staining, Masson's Trichrome (MT) staining, and tumor necrosis factor α (TNF-α), Ki-67, CD31, ERK1/2, and NF-κB immunohistochemical staining were performed. Results: The biodegradable and biocompatible hydrogel carries a homogenous interactive porous structure with 10 µm pore size and five weeks in vivo degradation time. The loaded Rg3 can be released sustainably. The in vitro cytotoxicity study showed that the hydrogel had no effect on survival rate of murine skin fibroblasts L929. The Rg3-loaded hydrogel can facilitate perianal ulcer healing by inhibiting local and systematic inflammatory responses, swelling the proliferation of nuclear cells, collagen deposition, and vascularization, and activating ERK signal pathway. Conclusion: The Rg3-loaded hydrogel shows the best treatment efficacy of perianal ulcer and may be a candidate for perianal ulcer treatment.

Case report of isolated synchronous multiple splenic metastases from rectal cancer: A case report and brief review of the literature.

INTRODUCTION: Isolated splenic metastasis emanating from colorectal cancer is an extremely rare finding, which usually indicates widely disseminated and multiple metastatic cancer. There have only been 39 cases of isolated splenic metastasis reported in the English literature to date. PATIENT CONCERNS: An 84-year-old female patient presented to our department with dark-red bloody stool that had persisted for 1 month and with an increased serum carcinoembryonic antigen (CEA) level. DIAGNOSES: A colonoscopy showed a rectal mass located 3 cm from the anal margin, which was 45 mm in diameter. The patient was diagnosed with rectal cancer with splenic metastases by abdomen computed tomography. INTERVENTIONS: The patient underwent a radical resection of rectal cancer and splenectomy, and the postoperative histopathology confirmed that the splenic lesions were derived from the adenocarcinoma of the rectum. OUTCOMES: After surgical treatment, the patient recovered well and was recommended for further chemotherapy. CONCLUSIONS: In addition to revealing a rare case, we also performed a literature review, including a brief discussion about the atypical isolated splenic metastasis from colorectal cancer. Our findings enrich the database of this rare clinical entity and provide experience in the management of splenic metastasis.

Role of Ginseng, Quercetin, and Tea in Enhancing Chemotherapeutic Efficacy of Colorectal Cancer.

As the most common gastrointestinal malignancy, colorectal cancer (CRC) remains a leading cause of cancer death worldwide. Although multimodal chemotherapy has effectively improved the prognosis of patients with CRC in recent years, severe chemotherapy-associated side effects and chemoresistance still greatly impair efficacy and limit its clinical application. In response to these challenges, an increasing number of traditional Chinese medicines have been used as synergistic agents for CRC administration. In particular, ginseng, quercetin, and tea, three common dietary supplements, have been shown to possess the potent capacity of enhancing the sensitivity of various chemotherapy drugs and reducing their side effects. Ginseng, also named "the king of herbs", contains a great variety of anti-cancer compounds, among which ginsenosides are the most abundant and major research objects of various anti-tumor studies. Quercetin is a flavonoid and has been detected in multiple common foods, which possesses a wide range of pharmacological properties, especially with stronger anti-cancer and anti-inflammatory effects. As one of the most consumed beverages, tea has become particularly prevalent in both West and East in recent years. Tea and its major extracts, such as catechins and various constituents, were capable of significantly improving life quality and exerting anti-cancer effects both in vivo and in vitro. In this review, we mainly focused on the adjunctive effects of the three herbs and their constituents on the chemotherapy process of CRC.

Therapeutic effects of ginseng and ginsenosides on colorectal cancer.

Colorectal cancer (CRC) is among the most common malignant diseases with high morbidity and mortality rates. Ginseng and its major extracts, ginsenosides, have been used in medical fields for thousands of years. In particular, their huge anti-cancer potential has drawn a great deal of attention in recent years. There is a large body of evidence that has shown that ginseng and its extracts could significantly inhibit tumor development and progression by suppressing cell proliferation, tumor growth, invasion and metastasis, inducing tumor cell apoptosis, regulating tumor-associated immune responses, and improving the therapeutic effect of chemotherapy. Notably, different subtypes of ginsenosides, even those extracted from the same ginseng, have exhibited distinct anti-cancer functions through different mechanisms. Over the past few years, a large number of studies have focused on how ginseng or various ginsenosides influence CRC development. Therefore, the roles and the potential of ginseng and ginsenosides in the treatment of CRC are summarized in this review. In addition, the biochemical properties of ginseng and ginsenosides are also briefly described.

Undifferentiated high-grade pleomorphic sarcoma of the colon: a rare case report and literature review.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma (MFH), hardly originates from the colorectum. CASE PRESENTATION: We reported a 65-year-old female presented with UPS in the descending colon. Computed tomography (CT) revealed an irregularly thickened descending colon. On colonoscopy examination, an ulcerative tumour was identified. The patient received radical resection of the left colon and partial enterectomy. The resected tumor was ulcerative, 10 cm × 8 cm × 5 cm in size, and infiltrated the serosa layer. Postsurgical pathology showed that the tumor was high-graded UPS in the colon with large amounts of necrotic tissues. CONCLUSIONS: UPS in the large intestine is a rare malignant tumor with a poor prognosis and unknown pathogenesis. The main treatment for UPS is early complete resection. Postsurgery adjuvant radiotherapy or chemotherapy can be attempted.

The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis.

BACKGROUND: Protective ileostomy is always applied to avoid clinically significant anastomotic leakage and other postoperative complications for patients receiving laparoscopic rectal cancer surgery. However, whether it is necessary to perform the ileostomy is still controversial. This meta-analysis aims to analyze the efficacy of ileostomy on laparoscopic rectal cancer surgery. METHODS: Cochrane Library, EMBASE, Web of Science, and PubMed were applied for systematic search of all relevant literature, updated to May 07, 2021. Studies compared patients with and without ileostomy for laparoscopic rectal cancer surgery. We applied Review Manager software to perform this meta-analysis. The quality of the non-randomized controlled trials was assessed using the Newcastle-Ottawa scale (NOS), and the randomized studies were assessed using the Jadad scale. RESULTS: We collected a total of 1203 references, and seven studies were included using the research methods. The clinically significant anastomotic leakage rate was significantly lower in ileostomy group (27/567, 4.76%) than that in non-ileostomy group (54/525, 10.29%) (RR = 0.47, 95% CI 0.30-0.73, P for overall effect = 0.0009, P for heterogeneity = 0.18, I2 = 32%). However, the postoperative hospital stay, reoperation, wound infection, and operation time showed no significant difference between the ileostomy and non-ileostomy groups. CONCLUSION: The results demonstrated that protective ileostomy could decrease the clinically significant anastomotic leakage rate for patients undergoing laparoscopic rectal cancer surgery. However, ileostomy has no effect on postoperative hospital stay, reoperation, wound infection, and operation time. The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis.

A rare case report of anal canal adenocarcinoma.

RATIONALE: Anal canal adenocarcinoma is a kind of rare malignant tumor of the intestinal tract with a low incidence rate. PATIENT CONCERNS: A 42-year-old man came to our department with anal tenderness accompanied by intermittent drainage of mucus discharge for 2 weeks. DIAGNOSES: The computer tomography showed a strip-shaped high-density shadow in the rectal wall. The magnetic resonance imaging showed a cyst-like mass of about 33 × 57 × 30 mm in the anal area. The lesion penetrated the anal canal, and plaque-shaped high signal shadow can be seen in the left side of the anus. The intraoperative pathology indicated the mass as anal canal adenocarcinoma. INTERVENTIONS: The abdominal perineal resection was performed for this patient. The postsurgical pathology showed that the tumor was anal canal adenocarcinoma with large amounts of mucus. OUTCOMES: The patient recovered well and was discharged from our department at 12th day post-surgery. This patient received further pelvic radiotherapy. LESSONS: Anal canal adenocarcinoma is a kind of malignant tumor that is extremely rare clinically. Computer tomography, magnetic resonance imaging, coloscopy, and histopathology are vital for the diagnosis of anal canal adenocarcinoma. Comprehensive treatment, including abdominal perineal resection, radiotherapy, and chemotherapy, is important for the treatment of anal canal adenocarcinoma.

The Relationship Between Mesenchymal Stem Cells and Tumor Dormancy.

Tumor dormancy, a state of tumor, is clinically undetectable and the outgrowth of dormant tumor cells into overt metastases is responsible for cancer-associated deaths. However, the dormancy-related molecular mechanism has not been clearly described. Some researchers have proposed that cancer stem cells (CSCs) and disseminated tumor cells (DTCs) can be seen as progenitor cells of tumor dormancy, both of which can remain dormant in a non-permissive soil/niche. Nowadays, research interest in the cancer biology field is skyrocketing as mesenchymal stem cells (MSCs) are capable of regulating tumor dormancy, which will provide a unique therapeutic window to cure cancer. Although the influence of MSCs on tumor dormancy has been investigated in previous studies, there is no thorough review on the relationship between MSCs and tumor dormancy. In this paper, the root of tumor dormancy is analyzed and dormancy-related molecular mechanisms are summarized. With an emphasis on the role of the MSCs during tumor dormancy, new therapeutic strategies to prevent metastatic disease are proposed, whose clinical application potentials are discussed, and some challenges and prospects of the studies of tumor dormancy are also described.

Mesenchymal stem cell-derived exosomes for gastrointestinal cancer.

Gastrointestinal (GI) malignancies, a series of malignant conditions originating from the digestive system, include gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. GI cancers have been regarded as the leading cancer-related cause of death in recent years. Therefore, it is essential to develop effective treatment strategies for GI malignancies. Mesenchymal stem cells (MSCs), a type of distinct non-hematopoietic stem cells and an important component of the tumor microenvironment, play important roles in regulating GI cancer development and progression through multiple mechanisms, such as secreting cytokines and direct interactions. Currently, studies are focusing on the anti-cancer effect of MSCs on GI malignancies. However, the effects and functional mechanisms of MSC-derived exosomes on GI cancer are less studied. MSC-derived exosomes can regulate GI tumor growth, drug response, metastasis, and invasion through transplanting proteins and miRNA to tumor cells to activate the specific signal pathway. Besides, the MSC-derived exosomes are also seen as an important drug delivery system and have shown potential in anti-cancer treatment. This study aims to summarize the effect and biological functions of MSC-derived exosomes on the development of GI cancers and discuss their possible clinical applications for the treatment of GI malignancies.