Spatiotemporal and Multilayer Trade Network Patterns of the Global Cobalt Cycle.

Recent years have witnessed increasing attempts to track trade flows of critical materials across world regions and along the life cycle for renewable energy and the low carbon transition. Previous studies often had limited spatiotemporal coverage, excluded end-use products, and modeled different life cycle stages as single-layer networks. Here, we integrated material flow analysis and complex network analysis into a multilayer framework to characterize the spatiotemporal and multilayer trade network patterns of the global cobalt cycle from 1988 to 2020. We found substantial growth and notable structural changes in global cobalt trade over the past 30 years. China, Germany, and the United States play pivotal roles in different layers and stages of the global cobalt cycle. The interlayer relationships among alloys, batteries, and materials are robust and continually strengthening, indicating a trend toward synergistic trade. However, cobalt ore-exporting countries are highly concentrated and rarely involved in later life cycle stages, resulting in the weakest relationship between the ore layer and other layers. This causes fluctuations and uncertainty in the global cobalt trade. Our model, linking industrial ecology, supply chain analysis, and network analysis, can be extended to other materials that are critical for the future green transition.

[Betulinic acid inhibits non-small cell lung cancer by repolarizing tumor-associated macrophages via mTOR signaling pathway].

The abnormal activation of the mammalian target of rapamycin(mTOR) signaling pathway in non-small cell lung cancer(NSCLC) is closely associated with distant metastasis, drug resistance, tumor immune escape, and low overall survival. The present study reported that betulinic acid(BA), a potent inhibitor of mTOR signaling pathway, exhibited an inhibitory activity against NSCLC in vitro and in vivo. CCK-8 and colony formation results demonstrated that BA significantly inhibited the viability and clonogenic ability of H1299, A549, and LLC cells. Additionally, the treatment with BA induced mitochondrion-mediated apoptosis of H1299 and LLC cells. Furthermore, BA inhibited the mobility and invasion of H1299 and LLC cells by down-regulating the expression level of matrix metalloproteinase 2(MMP2) and impairing epithelial-mesenchymal transition. The results demonstrated that the inhibition of mTOR signaling pathway by BA decreased the proportion of M2 phenotype(CD206 positive) cells in total macrophages. Furthermore, a mouse model of subcutaneous tumor was established with LLC cells to evaluate the anti-tumor efficiency of BA in vivo. The results revealed that the administration of BA dramatically retarded the tumor growth and inhibited the proliferation of tumor cells. More importantly, BA increased the ratio of M1/M2 macrophages in the tumor tissue, which implied the enhancement of anti-tumor immunity. In conclusion, BA demonstrated the inhibitory effect on NSCLC by repolarizing tumor-associated macrophages via the mTOR signaling pathway.

Tetrahydrocurcumin regulates the tumor immune microenvironment to inhibit breast cancer proliferation and metastasis via the CYP1A1/NF-κB signaling pathway.

The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

The impact of SARS-COV-2 infection on menstruation.

BACKGROUND: Recent study has demonstrated that the GnRH system in patients with post-COVID syndrome may be influenced by SARS-CoV-2. However, the impact of COVID-19 infection on women's menstruation is still unknown. OBJECTIVE: We aimed to investigate the the relationship between coronavirus disease 2019 (COVID-19) and menstruation in premenopausal women. METHODS: This was a retrospective cohort study. Pre-menopausal women were invited to participate in the online questionnaire on wechat. Participants were divided into four groups according to whether they were infected with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) and whether they had menstrual changes during the pandemic. Sociodemographic characteristics, history of COVID-19, menstruation and menstrual changes of the participants were collected. Statistical analyses were performed using SPSS, version 25.0 (SPSS Inc., Chicago, IL, USA). RESULTS: A total of 1946 women were included in the study. 1800 participants had been or were currently infected with SARS-COV-2, and 146 people had not been infected. Among 1800 patients with COVID-19, 666 (37.0%) had changes in menstruation, and 1134 (63.0%) did not, which was significantly higher than the uninfected participants (c2 = 12.161, P = 0.000). The proportion of participants with menstrual cycle changes (450/67.6%) is larger than that of uninfected participants (c2 = 6.904, P = 0.009). COVID-19 vaccination was associated with lower odds of menstrual cycle change (OR, 0.855; 95% CI, 0.750-0.976). Participants who reported chest pain (OR, 1.750, 95% CI, 1.209-2.533) and dyspnea (OR, 1.446; 95% CI, 1.052-1.988) during infection had greater odds of changes to their menstrual cycle compared with the participants who did not. CONCLUSIONS: The association between the COVID-19 and increased prevalence of menstrual cycle irregularity. COVID-19 vaccination is a protective factor in the long term, and participants with chest pain and dyspnea are more likely to develop AUB.

Clinical and metabolic characteristics of endometrial lesions in polycystic ovary syndrome at reproductive age.

BACKGROUND: We aimed to explore the clinical and metabolic characteristics in polycystic ovary syndrome (PCOS) patients with different endometrial lesions. METHODS: 234 PCOS patients who underwent hysteroscopy and endometrial biopsy were categorized into four groups: (1) normal endometrium (control group, n = 98), (2) endometrial polyp (EP group, n = 92), (3) endometrial hyperplasia (EH group, n = 33), (4) endometrial cancer (EC group, n = 11). Serum sex hormone levels, 75 g oral glucose tolerance test, insulin release test, fasting plasma lipid, complete blood count and coagulation parameters were measured and analyzed. RESULTS: Body mass index and triglyceride level of the EH group were higher while average menstrual cycle length was longer in comparison with the control and EP group. Sex hormone-binding globulin (SHBG) and high density lipoprotein were lower in the EH group than that in the control group. 36% of the patients in the EH group suggested obesity, higher than the other three groups. Using multivariant regression analysis, patients with free androgen index > 5 had higher risk of EH (OR 5.70; 95% CI 1.05-31.01), while metformin appeared to be a protective factor for EH (OR 0.12; 95% CI 0.02-0.80). Metformin and hormones (oral contraceptives or progestogen) were shown to be protective factors for EP (OR 0.09; 95% CI 0.02-0.42; OR 0.10; 95% CI 0.02-0.56). Hormones therapy appeared to be a protective factor for EC (OR 0.05; 95% CI 0.01-0.39). CONCLUSION: Obesity, prolonged menstrual cycle, decreased SHBG, and dyslipidemia are risk factors for EH in patients with PCOS. Oral contraceptives, progestogen and metformin are recommended for prevention and treatment of endometrial lesions in PCOS patients.

Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

Decoupling analysis between economic growth and aluminum cycle: From the perspective of aluminum use and carbon emissions.

Increasing aluminum demand under the clean energy and low-carbon transformation background increases the fuzziness of relationships between economic growth and aluminum use or aluminum related carbon emissions. To figure this out, this paper established an aluminum use and carbon emissions integrated decoupling model within the framework of anthropogenic aluminum cycle. A material flow analysis (MFA) during 2000-2020 for China's aluminum cycle was firstly conducted to quantify both aluminum flow and carbon emissions in each aluminum life-cycle process. Then, this paper evaluated and decomposed the decoupling index of aluminum use-economy and carbon emission-economy via the LMDI decomposition model. Results show that: (1) secondary aluminum has not become effective supplement for primary aluminum in China; (2) the expansive negative decoupling state was the most prevalent state. The decoupling effects of carbon emission were better than that of aluminum use; (3) technology improvement was an important impactor to decoupling process but didn't offset the growth in aluminum consumption or carbon emissions at most of the time. The government and industry organizers should implement active countermeasures to stimulate aluminum companies developing technology to improve aluminum use efficiency and reduce carbon emissions.

Regulatory function of DNA methylation mediated lncRNAs in gastric cancer.

As one of the most common malignancies worldwide, gastric cancer contributes to cancer death with a high mortality rate partly responsible for its out-of-control progression as well as limited diagnosis. DNA methylation, one of the epigenetic events, plays an essential role in the carcinogenesis of many cancers, including gastric cancer. Long non-coding RNAs have emerged as the significant factors in the cancer progression functioned as the oncogene genes, the suppressor genes and regulators of signaling pathways over the decade. Intriguingly, increasing reports, recently, have claimed that abnormal DNA methylation regulates the expression of lncRNAs as tumor suppressor genes in gastric cancer and lncRNAs as regulators could exert the critical influence on tumor progression through acting on DNA methylation of other cancer-related genes. In this review, we summarized the DNA methylation-associated lncRNAs in gastric cancer which play a large impact on tumor progression, such as proliferation, invasion, metastasis and so on. Furthermore, the underlying molecular mechanism and signaling pathway might be developed as key points of gastric cancer range from diagnosis to prognosis and treatment in the future.

[Mystery of Yiyin decoction theory: rule discovery and evaluation strategy of atypical pharmacological effects of Chinese medicinal prescription].

Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.

[Comparative study on anti-inflammatory effect of Lonicerae Japonicae Flos and Lonicerae Flos].

The aim of this paper was to observe the anti-inflammatory action and mechanism of Lonicerae Japonicae Flos extract and Lonicerae Flos extract in xylene-induced ear swelling experiment and lipopolysaccharide(LPS)-induced RAW264.7 cell inflammatory model. In vivo, xylene-induced mouse auricle swelling model was used to detect the auricle swelling degree and swelling inhibition rate of Lonicerae Japonicae Flos extract and Lonicerae Flos extract; the pathological changes of mice auricle were observed by hematoxylin eosin(HE) staining. In vitro, RAW264.7 inflammatory cell model was induced by LPS, where the cytotoxic effects of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on RAW264.7 cells were detected by CCK-8 method; Griess method was used to detect the effect of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on nitric oxide(NO) production, and ELISA method was used to detect the content of inflammatory factors interleukin-6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α). At last, Western blot was used to detect the protein changes of cyclooxygenase 1(COX1), COX2 and inducible nitric oxide synthetase(iNOS) for RAW264.7 cells. The results showed that both Lonicerae Japonicae Flos extract and Lonicerae Flos extract could significantly inhibit the degree of auricle swelling caused by xylene in mice and the inhibition rate was positively correlated with the drug dose. Furthermore, both of them could reduce the infiltration of lymphocytes and neutrophils in mouse ear tissues. For in vitro experiments, both Lonicerae Japonicae Flos extract and Lonicerae Flos extract inhibited NO secretion in RAW264.7 cells, down-regulated the release of IL-1ß, IL-6 and TNF-α, and down-regulated iNOS protein and COX2, NF-κB p65 protein content. In conclusion, both Lonicerae Japonicae Flos extract and Lonicerae Flos extract have good anti-inflammatory effect, and the mechanism may be related with the inhibition of NF-κB signaling pathway.

Nifuroxazide induces apoptosis, inhibits cell migration and invasion in osteosarcoma.

Osteosarcoma is the most common primary malignancy of bone and characterized by an appendicular primary tumor with a high rate of metastasis to the lungs. Unfortunately, there is no effective strategy to treat osteosarcoma in current clinical practice. In this study, the anticancer effects and potential mechanisms of nifuroxazide, an oral nitrofuran antibiotic, on two osteosarcoma cell lines were investigated. The results of the antiproliferative activity in vitro showed that nifuroxazide inhibited cell proliferation of UMR106 and MG63 cells in a dose- and time-dependent manner. Interestingly, nifuroxazide showed low toxicity to non-tumor cells (HEK 293 T). In addition, ROS-mitochondrial mediated apoptosis was observed after treatment of nifuroxazide. Moreover, nifuroxazide could significantly inhibit osteosarcoma cells migration and invasion via p-Stat3, MMP-2 and MMP-9 mediated signaling pathway. Taken together, our results suggested that nifuroxazide could be a promising agent for osteosarcoma treatment by inhibiting cell proliferation, inducing cell apoptosis and impairing cell migration and invasion.

Betulinic acid induces apoptosis and inhibits metastasis of human colorectal cancer cells in vitro and in vivo.

Betulinic acid (BA) is a pentacyclic triterpenoids extracted from birch with a wide range of biological properties. Recent studies have shown that BA has significant cytotoxicity to various types of human cancer cells, and shows potential in cancer treatment. However, the efficacy of BA on human colorectal cancer tumor cells is still unclear. The purpose of our study was to evaluate the anti-cancer activity of BA in human colorectal cancer cells in vitro and in vivo to investigate the possible mechanism. In this experiment, we found that BA inhibited colorectal cancer cell lines in vitro with a time-dependent and dose-dependent manner. Moreover, BA could induce cell apoptosis by upregulating expression of Bax and cleaved caspase-3 and downregulating protein of Bcl-2. BA could increase the production of reactive oxygen species and reduce mitochondrial membrane potential of cancer cell, suggesting that BA induced cancer cells apoptosis by mitochondrial mediated pathways. Furthermore, BA significantly inhibited the migration and invasion of colorectal cancer cells, reduced the expression of matrix metalloproteinase (MMPs) and increased the expression of MMPs inhibitor (TIMP-2). In addition, the growth of tumor was significantly suppressed by intraperitoneal administration of 20 mg/kg/day of BA in a xenograft tumor mouse model of HCT-116. Histopathological and immunohistochemical analysis showed that MMP-2+ cells and Ki-67+ cells were reduced and cleaved caspase-3+ cells were increased in tumor tissues of mice after BA administration. The results showed that BA not only promoted the apoptosis of colorectal cancer cells, but also inhibited the metastasis of cancer cells. Our results suggest that BA can be a potential natural drug to inhibit the growth and metastasis of colorectal cancer.

RhoA-stimulated intra-capillary morphology switch facilitates the arrest of individual circulating tumor cells.

Metastasis is the primary cause of death for most cancer patients. Hematogenous arrest of circulating tumor cells (CTCs) is an essential prerequisite for metastases formation. Using transparent transgenic zebrafish (kdrl:eGFP; Casper), together with resonant laser scanning confocal microscopy, we tracked the fate of CTCs in vivo in the blood circulation for days. We found the intra-capillary morphology-switch (ICMS) of individual CTCs from strip to sphere was necessary for their intravascular arrests. Further genetic and pharmacological inhibition experiments indicated that the RhoA signaling was necessary for ICMS and the arrest of CTCs. At last, we demonstrated that early treatment by a clinically approved RhoA/ROCK inhibitor, Fasudil, could efficiently inhibit the initial arrest of individual CTCs and reduce the incidence of tumor metastasis in both zebrafish and mouse models. These results together indicate that RhoA-stimulated ICMS represents a mechanism for the arrest of individual CTCs, providing a potential target for future treatments of hematogenous metastatic disease.

Regulatory function of glycolysis-related lncRNAs in tumor progression: Mechanism, facts, and perspectives.

Altered metabolism is a hallmark of cancer, and reprogramming of energy metabolism, known as the "Warburg effect", has long been associated with cancer. Cancer cells use the process of glycolysis to quickly manufacture energy from glucose, pyruvic acid, and lactate, which in turn accelerates the growth of cancer and glycolysis becomes a key target for anti-cancer therapies. Recent groundbreaking discoveries regarding long noncoding RNAs (lncRNAs) have opened a new chapter in the mechanism of cancer occurrence. It is widely recognized that lncRNAs regulate energy metabolism through glycolysis in cancer cells. LncRNAs have been demonstrated to engage in several cancer processes such as proliferation, apoptosis, migration, invasion, and chemoresistance, whereas glycolysis is enhanced or inhibited by the dysregulation of lncRNAs. As a result, cancer survival and development are influenced by different signaling pathways. In this review, we summarize the roles of lncRNAs in a variety of cancers and describe the mechanisms underlying their role in glycolysis. Additionally, the predictive potential of glycolysis and lncRNAs in cancer therapy is discussed.

Facts and prospects of peptide in targeted therapy and immune regulation against triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Due to the lack of specific therapeutic targets, treatment options are limited, and the recurrence and metastasis rate is high, the overall survival of patients is poor. However, with the discovery of some new targets and the corresponding immune regulation after targeting these targets, TNBC has a new hope in treatment. The peptide has a simple structure, strong binding affinity, and high stability, and has great potential in targeted therapy and immune regulation against TNBC. This review will discuss how single peptides and peptide combinations target triple-negative breast cancer to exert immunomodulatory effects. Among them, single peptides target specific receptors on TNBC cells, act as decoys to target key ligands in the regulatory pathway, and target TME-related cells. The combinations of peptides work in the form of cancer vaccines, engineered exosomes, microRNAs and other immune-related molecular pathways, immune checkpoint inhibitors, chimeric antigen receptor T cells, and drug-peptide conjugates. This article is mainly dedicated to exploring new treatment methods for TNBC to improve the curative effect and prolong the survival time of patients.

Unveiling the veil of lactate in tumor-associated macrophages: a successful strategy for immunometabolic therapy.

Lactate, traditionally regarded as a metabolic waste product at the terminal of the glycolysis process, has recently been found to have multifaceted functional roles in metabolism and beyond. A metabolic reprogramming phenomenon commonly seen in tumor cells, known as the "Warburg effect," sees high levels of aerobic glycolysis result in an excessive production of lactate. This lactate serves as a substrate that sustains not only the survival of cancer cells but also immune cells. However, it also inhibits the function of tumor-associated macrophages (TAMs), a group of innate immune cells ubiquitously present in solid tumors, thereby facilitating the immune evasion of malignant tumor cells. Characterized by their high plasticity, TAMs are generally divided into the pro-inflammatory M1 phenotype and the pro-tumour M2 phenotype. Through a process of 'education' by lactate, TAMs tend to adopt an immunosuppressive phenotype and collaborate with tumor cells to promote angiogenesis. Additionally, there is growing evidence linking metabolic reprogramming with epigenetic modifications, suggesting the participation of histone modification in diverse cellular events within the tumor microenvironment (TME). In this review, we delve into recent discoveries concerning lactate metabolism in tumors, with a particular focus on the impact of lactate on the function of TAMs. We aim to consolidate the molecular mechanisms underlying lactate-induced TAM polarization and angiogenesis and explore the lactate-mediated crosstalk between TAMs and tumor cells. Finally, we also touch upon the latest progress in immunometabolic therapies and drug delivery strategies targeting glycolysis and lactate production, offering new perspectives for future therapeutic approaches.

Dual inhibition of EGFR­VEGF: An effective approach to the treatment of advanced non­small cell lung cancer with EGFR mutation (Review).

On a global scale, the incidence and mortality rates of lung cancer are gradually increasing year by year. A number of bad habits and environmental factors are associated with lung cancer, including smoking, second­hand smoke exposure, occupational exposure, respiratory diseases and genetics. At present, low­dose spiral computed tomography is routinely the first choice in the diagnosis of lung cancer. However, pathological examination is still the gold standard for the diagnosis of lung cancer. Based on the classification and stage of the cancer, treatment options such as surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy are available. The activation of the EGFR pathway can promote the survival and proliferation of tumor cells, and the VEGF pathway can promote the formation of blood vessels, thereby promoting tumor growth. In non­small cell lung cancer (NSCLC) with EGFR mutation, EGFR activation can promote tumor growth by promoting VEGF upregulation through a hypoxia­independent mechanism. The upregulation of VEGF can make tumor cells resistant to EGFR inhibitors. In addition, the expression of the VEGF signal is also affected by other factors. Therefore, the use of a single EGFR inhibitor cannot completely inhibit the expression of the VEGF signal. In order to overcome this problem, the combination of VEGF inhibitors and EGFR inhibitors has become the method of choice. Dual inhibition can not only overcome the resistance of tumor cells to EGFR inhibitors, but also significantly increase the progression­free survival time of patients with NSCLC. The present review discusses the associations between the EGFR and VEGF pathways, and the characteristics of dual inhibition of the EGFR­VEGF pathway.

The role of peptides in reversing chemoresistance of breast cancer: current facts and future prospects.

Breast cancer is the first malignant tumor in women, and its incidence is also increasing year by year. Chemotherapy is one of the standard therapies for breast cancer, but the resistance of breast cancer cells to chemotherapy drugs is a huge challenge for the effective treatment of breast cancer. At present, in the study of reversing the drug resistance of solid tumors such as breast cancer, peptides have the advantages of high selectivity, high tissue penetration, and good biocompatibility. Some of the peptides that have been studied can overcome the resistance of tumor cells to chemotherapeutic drugs in the experiment, and effectively control the growth and metastasis of breast cancer cells. Here, we describe the mechanism of different peptides in reversing breast cancer resistance, including promoting cancer cell apoptosis; promoting non-apoptotic regulatory cell death of cancer cells; inhibiting the DNA repair mechanism of cancer cells; improving the tumor microenvironment; inhibiting drug efflux mechanism; and enhancing drug uptake. This review focuses on the different mechanisms of peptides in reversing breast cancer drug resistance, and these peptides are also expected to create clinical breakthroughs in promoting the therapeutic effect of chemotherapy drugs in breast cancer patients and improving the survival rate of patients.

Unlocking the potential of Mesenchymal stem cells in liver Fibrosis: Insights into the impact of autophagy and aging.

Liver fibrosis is a chronic liver disease characterized by extracellular matrix protein accumulation, potentially leading to cirrhosis or hepatocellular carcinoma. Liver cell damage, inflammatory responses, and apoptosis due to various reasons induce liver fibrosis. Although several treatments, such as antiviral drugs and immunosuppressive therapies, are available for liver fibrosis, they only provide limited efficacy. Mesenchymal stem cells (MSCs) have become a promising therapeutic option for liver fibrosis, because they can modulate the immune response, promote liver regeneration, and inhibit the activation of hepatic stellate cells that contribute to disease development. Recent studies have suggested that the mechanisms through which MSCs gain their antifibrotic properties involve autophagy and senescence. Autophagy, a vital cellular self-degradation process, is critical for maintaining homeostasis and protecting against nutritional, metabolic, and infection-mediated stress. The therapeutic effects of MSCs depend on appropriate autophagy levels, which can improve the fibrotic process. Nonetheless, aging-related autophagic damage is associated with a decline in MSC number and function, which play a crucial role in liver fibrosis development. This review summarizes the recent advancements in the understanding of autophagy and senescence in MSC-based liver fibrosis treatment, presenting the key findings from relevant studies.