A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-Inflammatory, and Anticancer Activities.

Curcumin, as the main active component of turmeric (Curcuma longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused on the antioxidant, anti-inflammatory, and anticancer effects of curcumin and its modified analogues. Exploring innovative curcumin derivatives offers promising strategies to address the challenges associated with its bioavailability and efficacy and valuable insights for future research directions.

A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.

Mitochondria and lysosomes play a very important role in maintaining cellular homeostasis, and the dysfunction of these organelles is closely related to many diseases. Recent studies have revealed direct interactions between mitochondria and lysosomes, forming mitochondria-lysosome contact sites that regulate organelle network dynamics and mediate the transport of metabolites between them. Impaired function of these contact sites is not only linked to physiological processes such as glucose and cholesterol transport but also closely related to the pathological processes of metabolic diseases. Here, we highlight the recent progress in understanding the mitochondria-lysosome contact sites, elucidate their role in regulating metabolic homeostasis, and explore the potential implications of this pathway in metabolic disorders.

The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: A promising therapeutic compound against the cytokine storm.

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 µM, 95% CI = 7.4 to 10.4 µM) was comparable to that of paracetamol (IC50 = 7.73 µM, 95% CI = 6.14 to 9.73 µM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.

Exploring the broad-spectrum pharmacological activity of two less studied Australian native fruits: chemical characterisation using LCMS-driven metabolomics.

Australian fruits such as native currant (Acrotriche depressa) and lemon aspen (Acronychia acidula) are under-examined in terms of their therapeutic potential. In this study, the in vitro antiproliferative activity of native currant and lemon aspen extracts (water and ethanol) against MCF7 breast adenocarcinoma cells was determined using the Alamar blue assay. The most potent extracts (native currant water, NC-W; native currant ethanol, NC-Et; lemon aspen ethanol, LA-Et) were further evaluated using flow cytometry to detect the potential induction of apoptosis in MCF7 cells whereas 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was implemented to understand the impact of the extracts on the intracellular reactive oxygen species (ROS) levels in MCF7 cells. Furthermore, the antioxidant activity of the extracts was assessed using ABTS [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate)], and CUPRAC (cupric reducing antioxidant capacity) assays. The antimicrobial susceptibility testing of NC-W, NC-Et, and LA-Et was carried out against Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli), and yeast (Candida albicans) strains using a resazurin-based assay. Additionally, potential metabolites in the NC-W and NC-Et extracts were analysed with liquid chromatography-mass spectrometry (LC-MS) driven metabolomics and chemometrics to spot differential and major metabolites. A dose-dependent antiproliferative activity was conferred by the NC extracts against MCF7 cells. Of the two LA extracts, only LA-Et showed a dose-dependent antiproliferative activity at higher concentrations. Both NC extracts and LA-Et induced apoptosis in MCF7 cells. None of the extracts increased the production of ROS significantly in MCF7 cells compared to the untreated control. A dose-dependent antioxidant activity was observed in both antioxidant assays. Both NC and LA extracts showed a similar minimum inhibitory concentration (MIC) value against S. aureus. Only LA-Et showed activity against E. coli, while NC-W and NC-Et were less active. All extracts showed MIC values of >1500 µg mL-1 against C. albicans. The metabolomics analysis revealed an abundance of flavonoids, fatty acyl derivatives, carbohydrates, carboxylic acids and their derivatives, and alkaloid compounds as potential bioactive metabolites in the NC extracts. In conclusion, both NC and LA showed antiproliferative (against MCF7 breast adenocarcinoma cells through the induction of apoptosis), strong antioxidant and minimal antimicrobial properties.

Identification of a distinct cluster of GDF15high macrophages induced by in vitro differentiation exhibiting anti-inflammatory activities.

Introduction: Macrophage-mediated inflammatory response may have crucial roles in the pathogenesis of a variety of human diseases. Growth differentiation factor 15 (GDF15) is a cytokine of the transforming growth factor-ß superfamily, with potential anti-inflammatory activities. Previous studies observed in human lungs some macrophages which expressed a high level of GDF15. Methods: In the present study, we employed multiple techniques, including immunofluorescence, flow cytometry, and single-cell RNA sequencing, in order to further clarify the identity of such GDF15high macrophages. Results: We demonstrated that macrophages derived from human peripheral blood mononuclear cells and rat bone marrow mononuclear cells by in vitro differentiation with granulocyte-macrophage colony stimulating factor contained a minor population (~1%) of GDF15high cells. GDF15high macrophages did not exhibit a typical M1 or M2 phenotype, but had a unique molecular signature as revealed by single-cell RNA sequencing. Functionally, the in vitro derived GDF15high macrophages were associated with reduced responsiveness to pro-inflammatory activation; furthermore, these GDF15high macrophages could inhibit the pro-inflammatory functions of other macrophages via a paracrine mechanism. We further confirmed that GDF15 per se was a key mediator of the anti-inflammatory effects of GDF15high macrophage. Also, we provided evidence showing that GDF15high macrophages were present in other macrophage-residing human tissues in addition to the lungs. Further scRNA-seq analysis in rat lung macrophages confirmed the presence of a GDF15high sub-population. However, these data indicated that GDF15high macrophages in the body were not a uniform population based on their molecular signatures. More importantly, as compared to the in vitro derived GDF15high macrophage, whether the tissue resident GDF15high counterpart is also associated with anti-inflammatory functions remains to be determined. We cannot exclude the possibility that the in vitro priming/induction protocol used in our study has a determinant role in inducing the anti-inflammatory phenotype in the resulting GDF15high macrophage cells. Conclusion: In summary, our results suggest that the GDF15high macrophage cells obtained by in vitro induction may represent a distinct cluster with intrinsic anti-inflammatory functions. The (patho)physiological importance of these cells in vivo warrants further investigation.

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells.

A growing body of literature underlines the fundamental role of gut microbiota in the occurrence, treatment, and prognosis of cancer. In particular, the activity of gut microbial metabolites (also known as postbiotics) against different cancer types has been recently reported in several studies. However, their in-depth molecular mechanisms of action and potential interactions with standard chemotherapeutic drugs remain to be fully understood. This research investigates the antiproliferative activities of postbiotics- short-chain fatty acid (SCFA) salts, specifically magnesium acetate (MgA), sodium propionate (NaP), and sodium butyrate (NaB), against the AGS gastric adenocarcinoma cells. Furthermore, the potential synergistic interactions between the most active SCFA salt-NaB and the standard drug dexamethasone (Dex) were explored using the combination index model. The molecular mechanisms of the synergy were investigated using reactive oxygen species (ROS), flow cytometry and biochemometric and liquid chromatography-mass spectrometry (LC-MS)-driven proteomics analyses. NaB exhibited the most significant inhibitory effect (p < 0.05) among the tested SCFA salts against the AGS gastric cancer cells. Additionally, Dex and NaB exhibited strong synergy at a 2:8 ratio (40 µg/mL Dex + 2,400 µg/mL NaB) with significantly greater inhibitory activity (p < 0.05) compared to the mono treatments against the AGS gastric cancer cells. MgA and NaP reduced ROS production, while NaB exhibited pro-oxidative properties. Dex displayed antioxidative effects, and the combination of Dex and NaB (2,8) demonstrated a unique pattern, potentially counteracting the pro-oxidative effects of NaB, highlighting an interaction. Dex and NaB individually and in combination (Dex:NaB 40:2400 µg/mL) induced significant changes in cell populations, suggesting a shift toward apoptosis (p < 0.0001). Analysis of dysregulated proteins in the AGS cells treated with the synergistic combination revealed notable downregulation of the oncogene TNS4, suggesting a potential mechanism for the observed antiproliferative effects. These findings propose the potential implementation of NaB as an adjuvant therapy with Dex. Further investigations into additional combination therapies, in-depth studies of the molecular mechanisms, and in vivo research will provide deeper insights into the use of these postbiotics in cancer, particularly in gastric malignancies.

Boosting regulatory T cell-dependent immune tolerance by activation of p53.

Regulatory T cells (Tregs) have critical roles in maintaining immune hemostasis and have important anti-inflammatory functions in diseases. Recently, we identified that CX-5461 (a selective RNA polymerase I inhibitor and p53 activator) acted as a potent immunosuppressive agent, which prevented allogeneic acute rejection in animal models via a molecular mechanism distinct from all those of conventional immunosuppressive drugs. Unexpectedly, we discovered that CX-5461 could promote Treg differentiation. In this review, we have summarized the evidence for a potential role of p53 in mediating Treg differentiation and its possible mechanisms, including regulation of FoxP3 transcription, regulation of the expression of PTEN (phosphatase and tensin homolog), as well as protein-protein interaction with the transcription factor STAT5 (signal transducer and activator of transcription 5). Evidence also suggests that pharmacological p53 activators may potentially be used to boost Treg-mediated immune tolerance. Based on these data, we argue that novel p53 activators such as CX-5461 may represent a distinct class of immunosuppressants that repress conventional T cell-mediated alloimmunity with concomitant boosting of Treg-dependent immune tolerance.

Mechanistic Insights into the Anti-Proliferative Action of Gut Microbial Metabolites against Breast Adenocarcinoma Cells.

The gut microbiota undergoes metabolic processes to produce by-products (gut metabolites), which play a vital role in the overall maintenance of health and prevention of disease within the body. However, the use of gut metabolites as anticancer agents and their molecular mechanisms of action are largely unknown. Therefore, this study evaluated the anti-proliferative effects of three key gut microbial metabolites-sodium butyrate, inosine, and nisin, against MCF7 and MDA-MB-231 breast adenocarcinoma cell lines. To determine the potential mechanistic action of these gut metabolites, flow cytometric assessments of apoptotic potential, reactive oxygen species (ROS) production measurements and proteomics analyses were performed. Sodium butyrate exhibited promising cytotoxicity, with IC50 values of 5.23 mM and 5.06 mM against MCF7 and MDA-MB-231 cells, respectively. All three metabolites were found to induce apoptotic cell death and inhibit the production of ROS in both cell lines. Nisin and inosine indicated a potential activation of cell cycle processes. Sodium butyrate indicated the possible initiation of signal transduction processes and cellular responses to stimuli. Further investigations are necessary to ascertain the effective therapeutic dose of these metabolites, and future research on patient-derived tumour spheroids will provide insights into the potential use of these gut metabolites in cancer therapy.

Neural Architecture Selection as a Nash Equilibrium With Batch Entanglement.

Modeling the architecture search process on a supernet and applying a differentiable method to find the importance of architecture are among the leading tools for differentiable neural architectures search (DARTS). One fundamental problem in DARTS is how to discretize or select a single-path architecture from the pretrained one-shot architecture. Previous approaches mainly exploit heuristic or progressive search methods for discretization and selection, which are not efficient and easily trapped by local optimizations. To address these issues, we formulate the task of finding a proper single-path architecture as an architecture game among the edges and operations with the strategies "keep" and "drop" and show that the optimal one-shot architecture is a Nash equilibrium of the architecture game. Then, we propose a novel and effective approach for discretizing and selecting a proper single-path architecture, which is based on extracting the single-path architecture that associates the maximal coefficient of the Nash equilibrium with the strategy "keep" in the architecture game. To further improve the efficiency, we employ a mechanism of entangled Gaussian representation of mini-batches, inspired by the classic Parrondo's paradox. If some mini-batch formed uncompetitive strategies, the entanglement of mini-batches would ensure the games be combined and, thus, turn into strong ones. We conduct extensive experiments on benchmark datasets and demonstrate that our approach is significantly faster than the state-of-the-art progressive discretizing methods while maintaining competitive performance with higher maximum accuracy.

Long-Term Complete Remission of a Patient With Double-Hit Diffuse Large B-Cell Lymphoma Treated by Chemoimmunotherapy and Chinese Herbal Medicine.

Double-hit diffuse large B-cell lymphoma (DHL) is an uncommon subtype of lymphoma which poorly responds to current drug therapies and has low rates of long-term survival in the patients. Herein, we report a case of a 73-year-old Caucasian male who was diagnosed with DHL with double-hit mutations of rearrangement of both c-MYC and BCL2 in November 2013. He commenced the standard R-CHOP-14 chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) but changed to dose-adjusted DA-EPOCH-R protocol (etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab) in the second and third cycles due to double-hit mutation. Because of intolerance to the intensive therapy, the patient decided to switch to Chinese medicine intervention. From March 2014 to December 2019, he was prescribed with a classical Chinese herbal formula-Sijunzi Decoction plus Prunella vulgaris based prescriptions. After 2 months of the Chinese herbal medicine intervention, the patient felt his right groin mass disappeared. Imaging follow-up showed no residual masses, and no lymphadenopathy was seen. During the period of Chinese herbal medicine treatment, his adherence and tolerability were well maintained with no adverse events. Imaging surveillances afterward found no evidence of lymphoma recurrence. His regular blood tests indicated that the patient's blood counts were normal and stable; no hematologic toxicity, hepatoxicity, or nephrotoxicity associated with Chinese herbal medicine were found. Follow-up visits until 2020 found that he had been living and enjoying a good quality of life for over 8 years post-diagnosis. This case study illustrates the potential values of Chinese herbal medicine in DHL treatment, alongside chemo-immunotherapy, and in maintaining long-term survival and satisfactory quality of life for DHL patients. The case report provides clinicians with preliminary evidence of the use of Chinese herbal medicine as a therapeutic strategy in the management of DHL.

The Fight against the Carcinogenic Epstein-Barr Virus: Gut Microbiota, Natural Medicines, and Beyond.

Despite recent advances in oncology, cancer has remained an enormous global health burden, accounting for about 10 million deaths in 2020. A third of the cancer cases in developing counties are caused by microbial infections such as human papillomavirus (HPV), Epstein-Barr Virus (EBV), and hepatitis B and C viruses. EBV, a member of the human gamma herpesvirus family, is a double-stranded DNA virus and the primary cause of infectious mononucleosis. Most EBV infections cause no long-term complications. However, it was reported that EBV infection is responsible for around 200,000 malignancies worldwide every year. Currently, there are no vaccines or antiviral drugs for the prophylaxis or treatment of EBV infection. Recently, the gut microbiota has been investigated for its pivotal roles in pathogen protection and regulating metabolic, endocrine, and immune functions. Several studies have investigated the efficacy of antiviral agents, gut microbial metabolites, and natural products against EBV infection. In this review, we aim to summarise and analyse the reported molecular mechanistic and clinical studies on the activities of gut microbial metabolites and natural medicines against carcinogenic viruses, with a particular emphasis on EBV. Gut microbial metabolites such as short-chain fatty acids were reported to activate the EBV lytic cycle, while bacteriocins, produced by Enterococcus durans strains, have shown antiviral properties. Furthermore, several natural products and dietary bioactive compounds, such as curcumin, epigallocatechin gallate, resveratrol, moronic acid, and andrographolide, have shown antiviral activity against EBV. In this review, we proposed several exciting future directions for research on carcinogenic viruses.

Trustworthy Deep Neural Network for Inferring Anticancer Synergistic Combinations.

The lack of a gold standard synergy quantification method for chemotherapeutic drug combinations warrants the consideration of different synergy metrics to develop efficient predictive models. Furthermore, neglecting combination sensitivity may lead to biased synergistic combinations, which are ineffective in cancer treatment. In this paper, we propose a deep learning-based model, SynPredict, which effectively predicts synergy in five synergy metrics together with the combination sensitivity score. SynPredict assesses the impact of multimodal fusion architectures of the input data, including the gene expression data of cancer cells, along with the representative chemical features of drugs in pairwise combinations. Both ONEIL and ALMANAC anticancer combination datasets are employed comparatively. The impact of the training datasets was more significant and consistent across most synergy models than input data fusion architectures. Synpredict outperforms the state-of-the-art predictive models, including DeepSynergy, AuDNN synergy, TranSynergy and DrugComb, with up to 74% decline in the mean square error. We highlight the pivotal need to consider a multiplex of synergy metrics and the combined sensitivity in the predictive models.

6-Shogaol and 10-Shogaol Synergize Curcumin in Ameliorating Proinflammatory Mediators via the Modulation of TLR4/TRAF6/MAPK and NFκB Translocation.

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokinesuppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-É£-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaol-curcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

Research Progress in Elucidating the Mechanisms Underlying Resveratrol Action on Lung Cancer.

Resveratrol has several functions, including protection of the heart and nervous system and exerts antidiabetic, anti-inflammatory, anti-aging, and antitumor effects. It is reported to impede the occurrence and development of tumors in cancer cell lines, animal models, and clinical studies. In vitro and in vivo experiments show that it exerts preventive or adjuvant therapeutic effects in pancreatic, colorectal, prostate, liver, and lung cancers. Mechanistic research reports show that resveratrol can induce tumor cell apoptosis and autophagy, inhibit cell cycle and angiogenesis, regulate nuclear factors and cyclooxygenase signal transduction pathways, and inhibit carcinogens' metabolic activation and alter tumor-related expression patterns; anti-oxidation affects tumor cell proliferation, metastasis, and apoptosis. However, the exact mechanism underlying its action remains unclear. This review highlights multiple aspects of the biological impacts and mechanisms underlying resveratrol action on the occurrence and development of lung cancer.

Australian native fruits and vegetables: Chemical composition, nutritional profile, bioactivity and potential valorization by industries.

Australian native plants have adapted themselves to harsh climatic conditions enabling them to produce unique and high levels of secondary metabolites. Native fruits and vegetables have been an integral part of the Indigenous Australian diet and Bush medicine for centuries. They have recently gained popularity owing to their rich dietary fiber, minerals, polyphenolic and antioxidant contents. This review presents a comprehensive summary and critical assessment of the studies performed in the last few decades to understand the phytochemical and nutritional profiles and therapeutic properties of Australian native fruits and vegetables. Furthermore, the potential of these fruits and vegetables as functional food ingredients and in the prevention and treatment of different diseases is discussed. Research on the nutritional and phytochemical profiles and therapeutic activity of Australian vegetables is limited with most studies focused on native fruits. These fruits have demonstrated promising antioxidant, anticancer, anti-inflammatory and antimicrobial activities mostly in in vitro models. More research to a) identify novel bioactive compounds, b) define optimal post-harvest and extraction methods, and c) understand molecular mechanisms of pharmacological activity through preclinical and clinical studies is prudent for the prospective and wider use of Australian native fruits and vegetables by the food, pharmaceutical, and nutraceutical industries.

Protective effect of the curcumin-baicalein combination against macrovascular changes in diabetic angiopathy.

Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats.

Preoperative Neutrophil to Lymphocyte Ratio Predicts Complications After Esophageal Resection That can be Used as Inclusion Criteria for Enhanced Recovery After Surgery.

Background: The neutrophil to lymphocyte ratio (NLR) has been reported as an indicator for poor prognosis in many cancers including esophageal cancer. However, the relationship between the NLR and postoperative complications after esophageal cancer resection remains unclear. At present, enhanced recovery after surgery (ERAS) lacks inclusion criteria. The aim of this study is to determine whether the preoperative NLR (preNLR) can predict complications after esophageal cancer resection, which could represent the criteria for ERAS. Methods: This was a retrospective study on 171 patients who underwent esophagectomy at Hospital between November 2020 and November 2021(68 patients from Changhai Hospital, 65 patients from Shanghai General Hospital and 38 patients from Affiliated Hospital of Qingdao University). Univariate and multivariate logistic regression analyses were performed to demonstrate that the preNLR could predict complications after esophagectomy. Results: A preNLR cutoff value of 2.30 was identified as having the greatest ability to predict complications with a sensitivity of 76% and specificity of 65%. Moreover, the Chi-squared test results showed that the preNLR was significantly associated with complications (x2 = 13.641, p < 0.001), and multivariate logistic regression analysis showed that body mass index (BMI), p stage and preNLR were independent variables associated with the development of postoperative complications (p < 0.05). Conclusion: The preNLR can predict complications after esophagectomy, and these predicted complications can represent the criteria for recruiting patients for ERAS.

Gut Metabolites and Breast Cancer: The Continuum of Dysbiosis, Breast Cancer Risk, and Potential Breast Cancer Therapy.

The complex association between the gut microbiome and cancer development has been an emerging field of study in recent years. The gut microbiome plays a crucial role in the overall maintenance of human health and interacts closely with the host immune system to prevent and fight infection. This review was designed to draw a comprehensive assessment and summary of recent research assessing the anticancer activity of the metabolites (produced by the gut microbiota) specifically against breast cancer. In this review, a total of 2701 articles were screened from different scientific databases (PubMed, Scopus, Embase and Web of Science) with 72 relevant articles included based on the predetermined inclusion and exclusion criteria. Metabolites produced by the gut microbial communities have been researched for their health benefits and potential anticancer activity. For instance, the short-chain fatty acid, butyrate, has been evaluated against multiple cancer types, including breast cancer, and has demonstrated anticancer potential via various molecular pathways. Similarly, nisin, a bacteriocin, has presented with a range of anticancer properties primarily against gastrointestinal cancers, with nominal evidence supporting its use against breast cancer. Comparatively, a natural purine nucleoside, inosine, though it has not been thoroughly investigated as a natural anticancer agent, has shown promise in recent studies. Additionally, recent studies demonstrated that gut microbial metabolites influence the efficacy of standard chemotherapeutics and potentially be implemented as a combination therapy. Despite the promising evidence supporting the anticancer action of gut metabolites on different cancer types, the molecular mechanisms of action of this activity are not well established, especially against breast cancer and warrant further investigation. As such, future research must prioritise determining the dose-response relationship, molecular mechanisms, and conducting animal and clinical studies to validate in vitro findings. This review also highlights the potential future directions of this field.