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Proactively programming materials toward target nonlinear mechanical behaviors is crucial to realize customizable functions for advanced devices and systems, which arouses persistent explorations for rapid and efficient inverse design strategies. Herein, we propose a "mechanical Fourier transform" strategy to program mechanical behaviors of materials by mimicking the concept of Fourier transform. In this strategy, an arbitrary target force-displacement curve is decomposed into multiple cosine curves and a constant curve, each of which is realized by a rationally designed multistable module in an array-structured metamaterial. Various target curves with distinct shapes can be rapidly programmed and reprogrammed through only amplitude modulation on the modules. Two exemplary metamaterials are demonstrated to validate the strategy with a macroscale prototype based on magnet lattice and a microscale prototype based on an etched silicon wafer. This strategy applies to a variety of scales, constituents, and structures, and paves a way for the property programming of materials.
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Colorectal cancer (CRC) is a significant public health concern, and its development is associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cancer cells owing to their plasticity and dynamic nature. The fusion-fission dynamics of mitochondria play a crucial role in signal transduction and metabolic functions of CRC cells. Enhanced mitochondrial fission promotes the metabolic reprogramming of CRC cells, leading to cell proliferation, metastasis, and chemoresistance. Excessive fission can also trigger mitochondria-mediated apoptosis. In contrast, excessive mitochondrial fusion leads to adenosine triphosphate (ATP) overproduction and abnormal tumor proliferation, whereas moderate fusion protects intestinal epithelial cells from oxidative stress-induced mitochondrial damage, thus preventing colitis-associated cancer (CAC). Therefore, an imbalance in mitochondrial dynamics can either promote or inhibit CRC progression. This review provides an overview of the mechanism underlying mitochondrial fusion-fission dynamics and their impact on CRC biology. This revealed the dual role of mitochondrial fusion-fission dynamics in CRC development and identified potential drug targets. Additionally, this study partially explored mitochondrial dynamics in immune and vascular endothelial cells in the tumor microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.
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Neoplasias Colorrectales , Dinámicas Mitocondriales , Humanos , Células Endoteliales/metabolismo , Mitocondrias/metabolismo , Transducción de Señal , Neoplasias Colorrectales/patología , Proteínas Mitocondriales/metabolismo , Microambiente TumoralRESUMEN
Colorectal cancer (CRC) is a common gastrointestinal malignancy with higher incidence and mortality rates in men compared to women, potentially due to the effects of estrogen signaling. There is substantial evidence supporting the significant role of 17ß-Estradiol (E2) in reducing CRC risk in females, although this perspective remains debated. E2 has been demonstrated to inhibit CRC cell proliferation and migration at the cellular level by enhancing DNA mismatch repair, modulating key gene expression, triggering cell cycle arrest, and reducing activity of migration factors. Furthermore, E2 contributes to promote a tumor microenvironment unfavorable for CRC growth by stimulating ERß expression, reducing inflammatory responses, reversing immunosuppression, and altering the gut microbiome composition. Conversely, under conditions of high oxidative stress, hypoxia, and nutritional deficiencies, E2 may facilitate CRC development through GPER-mediated non-genomic signaling. E2's influence on CRC involves the genomic and non-genomic signals mediated by ERß and GPER, respectively, leading to its dual roles in anticancer activity and carcinogenesis. This review aims to summarize the potential mechanisms by which E2 directly or indirectly impacts CRC development, providing insights into the phenomenon of sexual dimorphism in CRC and suggesting potential strategies for prevention and treatment.
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Neoplasias Colorrectales , Estradiol , Humanos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Estradiol/metabolismo , Animales , Receptor beta de Estrógeno/metabolismo , Receptor beta de Estrógeno/genética , Microambiente Tumoral , Transducción de SeñalRESUMEN
Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of 'microgenderome' and 'sex hormone-gut microbiome axis.' Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone-gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Femenino , Humanos , Masculino , Caracteres Sexuales , Hormonas Esteroides Gonadales , AndrógenosRESUMEN
BACKGROUND: Although there is numerous evidence on the epidemiological risk factors for insulin resistance (IR)-related metabolic diseases, there is still insufficient evidence to explore the non-linear association of Atherogenic Index of Plasma (AIP) with IR. Therefore, we aimed to elucidate the non-linear relationship between AIP and IR and type 2 diabetes (T2D). METHODS: This cross-sectional study was conducted in the National Health and Nutrition Survey (NHANES) from 2009 to 2018. A total of 9,245 participants were included in the study. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included IR and T2D defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, subgroup analysis, generalized additive model, smooth fitting curve and two-part logistic regression were adopted to reveal the relationship of AIP with IR and T2D. RESULTS: After adjustment for age, gender, race, education level, smoking status, alcohol consumption, vigorous/moderate physical activity, body mass index, waist circumference and hypertension, we found that AIP was positively associated with fasting blood glucose (ß = 0.08, 95% CI: 0.06, 0.10), glycosylated hemoglobin (ß = 0.04, 95% CI: 0.39, 0.58), fasting serum insulin (ß = 4.26, 95% CI: 3.73, 4.79), and homeostasis model assessment of insulin resistance (ß = 0.22, 95% CI: 0.18, 0.25). Further studies found that AIP was associated with increased risk of IR (OR = 1.29, 95% CI: 1.26-1.32) and T2D (OR = 1.18, 95% CI: 1.15-1.22). However, the positive association between AIP and IR or T2D was more significant in female than in male (IR: P for interaction = 0.0135; T2D: P for interaction = 0.0024). A non-linear and inverse L-shaped association was found between AIP and IR, while a J-shaped association was found between AIP and T2D. In patients with - 0.47 < AIP < 0.45, increased AIP was significantly associated with increased risk of IR and T2D. CONCLUSIONS: AIP showed an inverse L-shaped association with IR and a J-shaped association with T2D, indicating that AIP should be reduced to a certain level to prevent IR and T2D.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Femenino , Masculino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Encuestas Nutricionales , Factores de RiesgoRESUMEN
Natural fiber-reinforced biocomposites with excellent mechanical and biological properties have attractive prospects for internal medical devices. However, poor interfacial adhesion between natural silk fiber and the polymer matrix has been a disturbing issue for such applications. Herein, rigid-flexible agents, such as polydopamine (PDA) and epoxy soybean oil (ESO), were introduced to enhance the interfacial adhesion between Antheraea pernyi (Ap) silk and a common medical polymer, polycaprolactone (PCL). We compared two strategies of depositing PDA first (Ap-PDA-ESO) and grafting ESO first (Ap-ESO-PDA). The rigid-flexible interfacial agents introduced multiple molecular interactions at the silk-PCL interface. The "Ap-PDA-ESO" strategy exhibited a greater enhancement in interfacial adhesion, and interfacial toughening mechanisms were proposed. This work sheds light on engineering strong and tough silk fiber-based biocomposites for biomedical applications.
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Polímeros , Seda , PoliésteresRESUMEN
BACKGROUND Celastrol is extracted from the root of the Chinese traditional herb Tripterygium wilfordii, which has anti-cancer effects in multiple cancers. However, the effect of celastrol on the metastasis of triple-negative breast cancer and its mechanism remain largely unknown. MATERIAL AND METHODS MDA-MB-468 and MDA-MB-231 cells were treated with various doses of celastrol for 24 h. Cell viability was measured via MTT analysis. Cell migration and invasion were detected via transwell analysis. The expression of interleukin-6 (IL-6) was measured after transfection of short-hairpin RNA against IL-6 or celastrol treatment via quantitative real-time polymerase chain reaction, Western blot, or enzyme-linked immunosorbent analysis (ELISA). The protein levels in the nuclear factor-kappaB (NF-kappaB) pathway were measured by Western blot. The interaction between celastrol and NF-kappaB-mediated IL-6 was investigated by luciferase reporter assay. RESULTS High concentrations of celastrol inhibited viability of MDA-MB-468 and MDA-MB-231 cells, but low doses of celastrol showed little effect on cell viability. Low doses of celastrol suppressed cell migration and invasion, and knockdown of IL-6 also repressed cell migration and invasion. Moreover, treatment with celastrol decreased IL-6 expression at mRNA and protein levels. IL-6 overexpression mitigated celastrol-mediated suppression of cell migration and invasion. Additionally, celastrol blocked the NF-kappaB pathway to inhibit IL-6 levels. CONCLUSIONS Celastrol repressed migration and invasion through decreasing IL-6 levels by inactivation of NF-kappaB signaling in triple-negative breast cancer cells, providing a novel basis for use of celastrol in treating triple-negative breast cancer.
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Movimiento Celular/efectos de los fármacos , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Triterpenos Pentacíclicos/farmacología , Neoplasias de la Mama Triple Negativas/patología , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Humanos , Invasividad Neoplásica/patologíaRESUMEN
The incidence and mortality rates of colorectal cancer have elevated its status as a significant public health concern. Recent research has elucidated the crucial role of mitochondrial fusion-fission dynamics in the initiation and progression of colorectal cancer. Elevated mitochondrial fission or fusion activity can contribute to the metabolic reprogramming of tumor cells, thereby activating oncogenic pathways that drive cell proliferation, invasion, migration, and drug resistance. Nevertheless, excessive mitochondrial fission can induce apoptosis, whereas moderate mitochondrial fusion can protect cells from oxidative stress. This imbalance in mitochondrial dynamics can exert dual roles as both promoters and inhibitors of colorectal cancer progression. This review provides an in-depth analysis of the fusion-fission dynamics and the underlying pathological mechanisms in colorectal cancer cells. Additionally, it offers partial insights into the mitochondrial kinetics in colorectal cancer-associated cells, such as immune and endothelial cells. This review is aimed at identifying key molecular events involved in colorectal cancer progression and highlighting the potential of mitochondrial dynamic proteins as emerging targets for pharmacological intervention.
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Neoplasias Colorrectales , Dinámicas Mitocondriales , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine is increasingly used as complementary therapy to manage nausea and vomiting in different cultures. One such herbal recipe is the Hezhong granules, which contain classical antiemetic formulations, and are commonly used to prevent chemotherapy-induced nausea and vomiting (CINV). Modern pharmacological studies have shown that the key components of Hezhong granules, including Pinellia ternata (Thunb.), Evodia rutaecarpa (Juss.), and Zingiber officinale exhibit significant antiemetic and antitumor properties. Despite this promising evidence, controlling CINV remains a significant challenge in cancer treatment. Moreover, there is a lack of scientifically designed clinical trials to validate the efficacy and safety of classical antiemetic formulas for CINV interventions. AIMS OF THE STUDY: To investigate the efficacy and safety of Hezhong granules in preventing CINV in patients with advanced colorectal cancer (CRC). METHODS: This study was conducted between October 2020 and February 2022 in 12 hospital wards in Southwest China. In this multicenter, randomized controlled trial, we enrolled patients with advanced CRC who received fluorouracil-based chemotherapy. The patients were randomly assigned in a 1:1 ratio to either the Hezhong granule group (receiving a 5-HT3-receptor antagonist, dexamethasone, and Hezhong granules) or the placebo group (receiving a 5-HT3-receptor antagonist, dexamethasone, and placebo) during the first and second courses of chemotherapy. A 5-day diary was provided to all patients. Acute and delayed CINV were defined as CINV occurring within 24 h or between 24 and 120 h after the start of treatment. The primary endpoints were complete response rate (CRR, defined as the proportion of patients without nausea/vomiting) and objective response rate (ORR, defined as the proportion of patients without nausea/vomiting plus mild nausea/vomiting) for both acute and delayed CINV. Secondary endpoints were the daily rates of CINV events and Functional Living Index-Emesis (FLIE). To identify the predictors of CINV, we conducted multivariate ordered logistic regression analysis. This study was registered with the Chinese Clinical Trial, number ChiCTR2100041643. RESULTS: A total of 120 participants were randomly assigned, of whom 112 (56/56) completed two cycles and were included in the full analysis. In the acute phase, there were minor improvements in the Hezhong granule group, but there were no significant differences in the CRRs for nausea and vomiting (mean difference:10.7 %, P = 0.318, 0.324), while the ORRs increased by approximately 17.5 % (mean difference:16.1 %, P = 0.051; 17.9 %, P = 0.037, respectively). In the delayed phase, significant improvements of approximately 20 % were observed in both the CRRs (mean difference:19.6 %, P = 0.053; 21.4 %, P = 0.035) and ORRs (mean difference:17.9 %, P = 0.037, 0.043) for nausea and vomiting. Additionally, the daily rate of CINV events showed a mean difference of 19 % (P < 0.05). According to FLIE scores, approximately 70 % of patients who received Hezhong granules reported an improvement in their quality of life, with CINV symptoms having"no impact on daily life (NIDL)". No serious adverse events were attributed to herbal medicine. CONCLUSIONS: Hezhong granules proved to be both effective and well-tolerated in preventing CINV in patients with advanced CRC, with notable benefits in preventing delayed CINV. These promising results set the stage for subsequent phase III clinical trials and experimental research on Hezhong Granules.
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Antieméticos , Antineoplásicos , Neoplasias Colorrectales , Humanos , Antieméticos/uso terapéutico , Calidad de Vida , Estudios Prospectivos , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/tratamiento farmacológico , Dexametasona/uso terapéutico , Antineoplásicos/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inducido químicamente , Extractos Vegetales/uso terapéuticoRESUMEN
The prevalence of colorectal cancer is increasing worldwide, and despite advances in treatment, colorectal cancer (CRC) remains in the top three for mortality due to several issues, including drug resistance and low efficiency. There is increasing evidence that baicalin and baicalein, novel small molecule inhibitor extracts of the Chinese herb Scutellaria baicalensis, have better anti-colorectal cancer effects and are less likely to induce drug resistance in cancer cells. The present review article explains the anti-proliferative properties of baicalin and baicalein in the context of against CRC. Additionally, it explores the underlying mechanisms by which these compounds modulate diverse signaling pathways associated with apoptosis, cell proliferation, tumor angiogenesis, invasion, metastasis, and tumor microenvironment. Moreover, this review article highlights the inhibitory effect of colorectal inflammatory-cancer transformation and the near-term therapeutic strategy of using them as adjuvant agents in chemotherapy.
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Introduction: The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action. Materials and Methods: The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5). Results: A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = -1.84, 95% CI -2.14 to -1.55, P < 0.00001). It also reduced the percentage of cerebral infarction (SMD = -2.97, 95% CI -3.58 to -2.36, P < 0.00001) and brain water content (SMD = -2.37, 95% CI -3.63 to -1.12, P = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = -7.53, 95% CI -11.34 to -3.72, P = 0.0001), IL-1ß (SMD = -2.65, 95% CI -3.87 to -1.44, P < 0.0001), and IL-6 (SMD = -5.55, 95% CI -9.32 to -1.78, P = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, P = 0.0003), NOS (SMD = -1.52, 95% CI -2.98 to -0.06, P = 0.04), MDA (SMD = -5.31, 95% CI -8.48 to -2.14, P = 0.001), and NO (SMD = -5.33, 95% CI -8.82 to -1.84, P = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = -5.21, 95% CI -7.47 to -2.94, P < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, P < 0.0001). Conclusion: Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.
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The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.
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Materiales Biocompatibles , Regeneración Ósea , Fibroínas , Magnesio , Células Madre Mesenquimatosas , Osteogénesis , Andamios del Tejido , Fibroínas/química , Fibroínas/farmacología , Regeneración Ósea/efectos de los fármacos , Animales , Andamios del Tejido/química , Masculino , Osteogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratas , Magnesio/química , Magnesio/farmacología , Materiales Biocompatibles/química , Osteoblastos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratas Sprague-Dawley , Agua/química , Proliferación Celular/efectos de los fármacos , Ingeniería de Tejidos/métodos , Cráneo/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , BombyxRESUMEN
Objectives: To perform a meta-analysis and network analysis identification to evaluate the efficacy, safety, and potential mechanisms of modified Baitouweng decoction (mBTWD) in the treatment of radiation enteritis. Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Databases, SionMed, and Chinese Scientific Journals Database to collect the randomized controlled trials (RCTs) of mBTWD treating radiation enteritis. Rev.Man 5.3 and Stata 14.0 software are employed for meta-analysis. The GRADE online tool is used to evaluate the quality of evidence. Network analysis and molecular docking approach are applied to predict the potential targets and ingredients of representative drugs in mBTWD for the treatment of radiation enteritis. Results: Seventeen studies are eventually included, covering a total of 1611 patients: (1) The clinical efficacy is significantly higher in mBTWD groups than in control groups (RR = 1.24, 95% CI (1.17, 1.32), P < 0.00001). (2) mBTWD has certain advantages in improving TCM syndromes (MD = -3.41, P < 0.00001). (3) mBTWD has a certain positive effect on the improvement of intestinal signs and symptoms (RR = 1.23, P=0.0001; OR = 3.51, P < 0.00001). (4) Indexes including CRP, KPS, and OB, are better in mBTWD groups than in control groups (P < 0.00001, P=0.002, P=0.03), but the credibility is downgraded for a small sample size. Adverse events and recurrence rates require further confirmation with larger sample sizes. (5) Univariate meta-regression for clinical efficacy shows none of the coefficients are significantly associated with the estimated risk ratio. The clinical efficacy overestimates about 4.9% from publication bias. The quality of the included studies is low according to GRADE evidence. (6) Quercetin, isorhamnetin, and beta-sitosterol are the main ingredients from representative drugs in mBTWD and its key targets are MYC, TP53, and MAPK14/MAPK1. Conclusions: mBTWD may be effective in the treatment of radiation enteritis, but its long-term benefits, safety, and molecular mechanisms remain unclear due to the poor quality of the evidence. Larger sample sizes, high-quality studies, and basic research are essential in the future.
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Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) is the leading cause of cancer death in women. For patients with HER2-positive MBC, after the failure of multiple lines of treatment, there is no optimal line of therapy. A series of clinical trials confirmed that treatment with irreversible pan-HER tyrosine kinase inhibitors (TKIs) in combination with chemotherapy significantly improves patients' survival outcomes. This review focuses on the pathogenesis of HER2-positive breast cancer, current standard treatments, mechanisms of approved irreversible TKIs, and key clinical trials. The available findings suggest that irreversible pan-HER TKIs, such as pyrotinib and neratinib, in combination with chemotherapy, represent a beneficial salvage therapy for patients with HER2-positive MBC with manageable toxicity. However, further studies are needed to assess the efficacy and safety of this combination therapy.
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Colorectal cancer (CRC) is a common cancer worldwide with poor prognosis. The presence of Fusobacterium nucleatum (Fn) in the intestinal mucosa is associated with the progression of CRC. In this review, we explore the mechanisms by which Fn contributes to proliferation and migration of CRC cells from the following four aspects: induction of the epithelial-mesenchymal transition (EMT), regulation of the tumor microenvironment (TME), expression of oncogenic noncoding RNAs, and DNA damage. This review outlines the scientific basis for the use of Fn as a biomarker and therapeutic target in CRC.
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With the sharp change in our diet and lifestyle, the incidence of colorectal cancer (CRC) is increasing among young people and has become the second most common malignant tumor worldwide. Although the current treatment of CRC is getting updated rapidly, recurrence and metastasis are still inevitable. Therefore, new anticancer drugs are needed to break existing limitations. In recent years, Hedyotis diffusa Willd (HDW) extracts have been proved to demonstrate excellent anti-colorectal cancer effects and have been widely used in clinical practices. In this review, we aim to explore the advantages, potential signaling pathways, and representative active ingredients of HDW in the treatment of CRC from the perspective of molecular mechanism, in order to provide new ideas for the future treatment of CRC.
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Stimulating antitumor immunity is an attractive idea for suppressing tumors. CD4 + and CD8 + T cells as well as natural killer cells (NK) are the primary antitumor immune cells in the tumor microenvironment (TME). In contrast to these cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) release several molecules to suppress antitumor immunity and stimulate cancer cell invasion and proliferation. Adjuvant treatment with certain nontoxic agents is interesting to boost antitumor immunity. Metformin, which is known as an antidiabetes drug, can modulate both antitumor and protumor immune cells within TME. It has the ability to induce the proliferation of CD8 + T lymphocytes and NK cells. On the other hand, metformin attenuates polarization toward TAMs, CAFs, and Tregs. Metformin also may stimulate the antitumor activity of immune system cells, while it interrupts the positive cross-talk and interactions between immunosuppressive cells and cancer cells. The purpose of this review is to explain the basic mechanisms for the interactions and communications between immunosuppressive, anti-tumoral, and cancer cells within TME. Next, we discuss the modulating effects of metformin on various cells and secretions in TME.
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Objective: To systematically review the efficacy and safety of botanical drugs in the treatment of cancer-related fatigue (CRF) caused by gastric cancer (GC) and to determine the underlying pharmacological mechanisms using a network analysis. Methods: Databases such as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) from inception to 18 April 2022. Methodological quality assessment was performed using the collaborative tool Cochrane, and data analysis were carried out using RevMan 5.4 and STATA 16 software. The botanical drugs with the highest frequency of use in the included studies was selected. The chemical composition, targets of action, disease targets, and shared targets of these botanical drugs were screened based on network analysis to explore the potential mechanisms of treating CRF in patients with gastric cancer (GC). Results: A total of 13 studies that included 986 patients with gastric CRF met the inclusion criteria. The results showed that botanical drugs could improve the CRF scores of gastric CRF, including the total scores of CRF dichotomous data [Odds Ratio (OR) = 4.22; 95% confidence interval (CI) 1.67-10.68; p = 0.002], the total scores of CRF continuous data [Standardized Mean Difference (SMD) = -0.98; 95% CI -1.36 to -0.60; p < 0.00001], the affective subscales of Piper Fatigue Scale (PFS) scores [Weighted Mean Difference (MD) = -0.79; 95%CI -0.92 to -0.65; p < 0.00001], the sensory subscales of PFS scores (MD = -0.57; 95%CI -0.77 to -0.37; p < 0.00001), the behavioral subscales of PFS scores (MD = -1.05; 95% CI -1.29 to -0.82; p < 0.00001), Quality of Life Questionnaire Core 30 (QLQ-C30) (MD = 10.53, 95% CI 8.26 to12.80; p < 0.00001), and the Karnofsky Performance Status scale (KPS) (MD = 5.18, 95% CI 2.60 to 7.76; p < 0.0001). The botanical drugs group had milder adverse effects than the control group. A total of 44 chemical components and 241 potential targets were obtained from the online database and 121 drug targets overlapped with the disease targets of CRF in patients with GC. Moreover, five key active ingredients, namely quercetin, Stigmasterol, luteolin, kaempferol, and isorhamnetin, as well as five key targets including AKT1, TP53, TNF, VEGFA, and CASP3, were screened. In addition, five key signaling pathways, including cancer, Hepatitis B, Prostate cancer, Hepatitis C, and Pancreatic cancer pathways, were obtained through enrichment analysis. Conclusion: The results of the study showed that botanical drugs have positive effects on CRF in patients with GC. However, more well-designed, multicenter, and large sample-sized Randomized Controlled Trials are required to evaluate the effectiveness of botanical drugs on CRF in patients with GC.