Protective effects of Ganoderma lucidum spores on estradiol benzoate-induced TEC apoptosis and compromised double-positive thymocyte development.

Backgroud: Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of Ganoderma lucidum spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive. Methods: In this study, a mice model of estradiol benzoate (EB)-induced thymic atrophy was constructed, and the improvement effect of GLS on thymic atrophy was evaluated. Then, we employs multi-omics techniques to elucidate how GLS modulates T cell development amidst EB-induced thymic atrophy in mice. Results: GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4+ T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) α rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased Vα14-Jα18 rearrangement fosters double-positive (DP) to invariant natural killer T (iNKT) cell differentiation, partially contingent on RGLS-mediated restriction of peptide-major histocompatibility complex I (pMHCⅠ)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4+ iNKT cell development. Furthermore, RGLS amplifies interaction between a DP subpopulation, termed DPsel-7, and plasmacytoid dendritic cells (pDCs), likely facilitating the subsequent development of double-negative iNKT1 cells. Lastly, RGLS suppresses EB-induced upregulation of Abpob and Apoa4, curbing the clearance of CD4+Abpob+ and CD4+Apoa4+ T cells by mTECs, resulting in enhanced CD4+ T cell output. Discussion: These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS's immunoregulatory role pave the way for its potential as a T-cell regeneration inducer.

Icariside I enhances the effects of immunotherapy in gastrointestinal cancer via targeting TRPV4 and upregulating the cGAS-STING-IFN-I pathway.

Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy. In this study, we describe a previously unreported potentiating effect of Icariside I (ICA I, GH01), the main bioactive compound isolated from the Epimedium species, on anti-tumor immune responses. Mechanistically, molecular docking and SPR assay result show that ICA I binding with TRPV4. ICA I induced intracellular Ca2+ increasing and mitochondrial DNA release by targeting TRPV4, which triggered cytosolic ox-mitoDNA release. Importantly, these intracellular ox-mitoDNA fragments were taken up by immune cells in the tumor microenvironment, which amplified the immune response. Moreover, our study shows the remarkable efficacy of sequential administration of ICA I and anti-α-PD-1 mAb in advanced tumors and provides a strong scientific rationale for recommending such a combination therapy for clinical trials. ICA I enhanced the anti-tumor effects with PD-1 inhibitors by regulating the TRPV4/Ca2+/Ox-mitoDNA/cGAS/STING axis. We expect that these findings will be translated into clinical therapies, which will benefit more patients with cancer in the near future.

SCD1 promotes the stemness of gastric cancer stem cells by inhibiting ferroptosis through the SQLE/cholesterol/mTOR signalling pathway.

Cancer stem cells (CSCs) play a substantial role in cancer onset and recurrence. Anomalous iron and lipid metabolism have been documented in CSCs, suggesting that ferroptosis, a recently discovered form of regulated cell death characterised by lipid peroxidation, could potentially exert a significant influence on CSCs. However, the precise role of ferroptosis in gastric cancer stem cells (GCSCs) remains unknown. To address this gap, we screened ferroptosis-related genes in GCSCs using The Cancer Genome Atlas and corroborated our findings through quantitative polymerase chain reaction and western blotting. These results indicate that stearoyl-CoA desaturase (SCD1) is a key player in the regulation of ferroptosis in GCSCs. This study provides evidence that SCD1 positively regulates the transcription of squalene epoxidase (SQLE) by eliminating transcriptional inhibition of P53. This mechanism increases the cholesterol content and the elevated cholesterol regulated by SCD1 inhibits ferroptosis via the mTOR signalling pathway. Furthermore, our in vivo studies showed that SCD1 knockdown or regulation of cholesterol intake affects the stemness of GCSCs and their sensitivity to ferroptosis inducers. Thus, targeting the SCD1/squalene epoxidase/cholesterol signalling axis in conjunction with ferroptosis inducers may represent a promising therapeutic approach for the treatment of gastric cancer based on GCSCs.

NIR Absorbing Organic Chromophores Combination with NSAIDs for Remodeling of the Inflammatory Microenvironment to Amplify Tumor Ferroptosis-Photothermal Synergistic Therapy.

Photothermal therapy has emerged as a promising approach for cancer treatment, which can cause ferroptosis to enhance immunotherapeutic efficacy. However, excessively generated immunogenicity will induce serious inflammatory response syndrome, resulting in a discounted therapeutic effect. Herein, a kind of NIR absorption small organic chromophore nanoparticles (TTHM NPs) with high photothermal conversion efficiency (68.33%) is developed, which can induce mitochondria dysfunction, generate mitochondrial superoxide, and following ferroptosis. TTHM NPs-based photothermal therapy is combined with Sulfasalazine (SUZ), a kind of nonsteroidal anti-inflammatory drugs, to weaken inflammation and promote ferroptosis through suppressing glutamate/cystine (Glu/Cys) antiporter system Xc- (xCT). Additionally, the combination of SUZ with PTT can induce immunogenic cell death (ICD), followed by promoting the maturation of DCs and the attraction of CD8+ T cell, which will secrete IFN-γ and trigger self-amplified ferroptosis via inhibiting xCT and simulating Acyl-CoA synthetase long-chain family member 4 (ACSL4). Moreover, the in vivo results demonstrate that this combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation, facilitate T-cell infiltration, and realize effective thermal elimination of primary tumors and distant tumors. In general, this work provides an excellent example of combined medication and stimulates new thinking about onco-therapy and inflammatory response.

Metabolome classification of olive by-products from different oil presses providing insights into its potential health benefits and valorization as analyzed via multiplex MS-based techniques coupled to chemometrics.

INTRODUCTION: The Olive (Olea europaea L.) is one of the most popular edible oil-producing fruits, consumed worldwide for its myriad nutritional and health benefits. Olive oil production generates huge quantities of by-products from the fruit, which are considered environmental hazards. Recently, more and more efforts have been made to valorize olive by-products as a source of low-cost, value-added food applications. OBJECTIVE: The main objective of this study was to globally assess the metabolome of olive fruit by-products, including olive mill wastewater, olive pomace, and olive seeds from fruits from two areas, Siwa and Anshas, Egypt. METHODS: Gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography with mass spectrometry (UPLC-MS) were used for profiling primary and secondary metabolites in olive by-products. Also, multivariate data analyses were used to assess variations between olive by-product samples. RESULTS: A total of 103 primary metabolites and 105 secondary metabolites were identified by GC-MS and UPLC-MS, respectively. Fatty acids amounted to a major class in the olive by-products at 53-91%, with oleic acid dominating, especially in the pomace of Siwa. Mill wastewater was discriminated from other by-products by the presence of phenolics mainly tyrosol, hydroxyl tyrosol, and α-tocopherol as analyzed by UPLC-MS indicating their potential antioxidant activity. Pomace and seeds were rich in fatty acids/esters and hydroxy fatty acids and not readily distinguishable from each other. CONCLUSION: The current work discusses the metabolome profile of olive waste products for valorization purposes. Pomace and seeds were enriched in fatty acids/esters, though not readily distinguishable from each other.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Structure characteristics, protective effect and mechanisms of ethanol-fractional polysaccharides from Dendrobium officinale on acute ethanol-induced gastritis.

Gastritis is a common disease characterized by gastric ulcers and severe bleeding. Excessive daily alcohol consumption can cause acute gastritis, impacting individuals' quality of life. This study aims to explore the protective effects of different ethanol-fractional polysaccharides of Dendrobium officinale (EPDO) on acute alcohol-induced gastric injury in vivo. Results showed that EPDO-80, identified as a ß-glucan, exhibited significant anti-inflammatory properties in pathology. It could reduce the area of gastric mucosal injury and cell infiltration. EPDO-80 had a dose-effect relationship in reducing the levels of malondialdehyde and cyclooxygenase-2 and decreasing the levels of inflammation mediators such as tumor necrosis factor α. More extensively, EPDO-80 could inhibit the activation of the TNFR/IκB/NF-κB signaling pathway, reducing the production of TNF-α mRNA and cell apoptosis in organs. Conversely, EPDO-80 could promote changes in the gut microbiota structure. These findings suggest that EPDO-80 could have great potential in limiting oxidative stress and inflammation mediated by inhibiting the NF-κB signaling pathway, which is highly related to its ß-glucan structure and functions in gut microbiota.

[Research progress in surgical treatment of avascular necrosis of talus].

Objective: To summarize the surgical treatment methods for avascular necrosis of the talus. Methods: The recent domestic and international literature related to avascular necrosis of the talus was extensively conducted. The pathogenesis, surgical treatment methods, and prognosis were summarized. Results: The clinical symptoms of avascular necrosis of the talus at early stage are not obvious, and most patients have progressed to Ficat-Arlet stages Ⅲ-Ⅳ and require surgical treatment. Currently, surgical treatments for this disease include core decompression, vascularized bone flap transplantation, arthroplasty, and arthrodesis, etc. Early avascular necrosis of the talus can be treated conservatively, and if treatment fails, core decompression can be considered. Arthrodesis is a remedial surgery for patients with end-stage arthritis and collapse, and in cases of severe bone loss, tibiotalocalcaneal arthrodesis and bone grafting are required. Vascularized bone flap transplantation is effective and plays a role in all stages of avascular necrosis of the talus, but the appropriate donor area for the flap still needs further to be studied. Conclusion: The surgical treatment and the system of treatment for different stages of avascular necrosis of the talus still need to be refined.

Assessing the Feasibility and Safety of the Toumai® Robotic System in Urologic Surgery: Initial Experience.

Introduction: Robotic surgery using da Vinci surgical system has gained prominence in urology; emerging robotic platforms are expanding its applications and increasing affordability. We assess the feasibility and safety of a novel system, the Toumai® robotic system in various urological surgeries. Methods: This prospective study was conducted at the first affiliated hospital of Zhengzhou university. Twenty consecutive patients underwent renal and prostatic surgery with the Toumai. The study assessed technical feasibility (conversion rate) and safety (perioperative complications) of the procedures as primary outcomes. Secondary endpoints included key surgical perioperative outcomes: functional and oncologic results. The Endoscopic Surgical System operates within a master-slave protocol, comprising a Surgeon Console, Patient Platform, and Vision Platform. Results: Seventeen patients underwent various nephrectomy procedures and three underwent radical prostatectomy (RP). There was no conversion to alternative surgical approach; a single (Clavien-Dindo grade ≥3b) complication occurred, and no readmission was recorded within 30 days. The median operative time was 120, 140, and 210 minutes for partial nephrectomy (PN), radical nephrectomy, and RP, respectively. Off-clamp PN was performed in one case, and the warm ischemia time in the remaining two case was 18 minutes. The median docking time was 22 minutes for nephrectomy and 20 minutes for RP; no major robotic malfunction was encountered. At 3-month follow-up, no tumor recurrence was recorded, renal function was well preserved, and the continence status was satisfactory. Conclusions: We present the initial clinical utilization of an innovative robotic platform. Complex urological surgeries were successfully completed without conversions and with minimal complications. Further investigations are warranted to confirm these initial findings.

Comparative pharmacokinetic analysis of sporoderm-broken and sporoderm-removed Ganoderma lucidum spore in rat by using a sensitive plasma UPLC-QqQ-MS method.

Previous studies have found that removing the sporoderm significantly enhanced antitumor and immunoregulatory activities of Ganoderma lucidum spore (GLS) compared with breaking the sporoderm. However, the pharmacokinetics of sporoderm-removed GLS (RGLS) and sporoderm-broken GLS (BGLS) remain elusive. To compare the pharmacokinetic differences between the two products, we developed a UPLC-QqQ MS method for determining nine representative triterpenoid concentrations. Chloramphenicol was used as an internal standard. The samples were separated on a reversed-phase column using acetonitrile-0.1% formic acid and water-0.1% formic acid as mobile phases. Nine triterpenoids were analyzed using multiple reaction monitoring mode. The results showed that the area under the concentration-time curve from dosing to time t of all nine components was increased in RGLS compared with BGLS. And the time to the maximum concentration in BGLS was delayed compared with that of RGLS. These indicated that the absorption of RGLS was better than that of BGLS, and the sporoderm might hinder the absorption of the active components. These results increase our understanding of the bioavailability of BGLS and RGLS and indicate that increased bioavailability is one of the main reasons for the enhanced efficacy of RGLS.

Estimating the Change in Facial Subunits During Positive and Negative Facial Expression Using Three-Dimensional Stereophotogrammetry Facial Analysis.

Background: A more refined and clinically related facial expression analysis is required for patients who wish to be perceived more emotionally positive. Objective: To measure the change in skin vector and volume in facial subunits when expressing positive expression (happiness) compared with negative expressions (sadness, fear, disgust, and anger), using three-dimensional (3D) stereophotogrammetry analysis. Methods: This study took 3D photographs of 20 volunteers' face at rest and during positive and negative expression. The directions of skin vector and volume changes in each facial subregion were recorded and calculated. Results: In the positive expression, 78.3% (95% confidence interval [CI] 66.8-89.9) of the medial midfacial subregions presented superolateral vector and volume increase, whereas volume decrease in 82.5% (95% CI 78.5-86.5) of the lip subregions could be observed. In the negative expression, the vector changes were predominantly inferomedial in 26.0% (95% CI 15.4-36.5) of the forehead and 36.8% (95% CI 33.2-40.3) of the upper eyelid subregions, whereas volume increases in 34.0% (95% CI 30.4-37.7) of the upper eyelid subregions were observed. Conclusions: This 3D stereophotogrammetry analysis presents the morphological difference between the positive and negative expression.

Advances in the Application of Bone Transport Techniques in the Treatment of Bone Nonunion and Bone Defects.

Bone nonunion and bone defects frequently occur following high-energy open injuries or debridement surgeries, presenting complex challenges to treatment and significantly affecting patients' quality of life. At present, there are three primary treatment options available for addressing bone nonunion and bone defects: vascularized bone grafts, the Masquelet technique, and the Ilizarov technique. The Ilizarov technique, also known as distraction osteogenesis, is widely favored by orthopedic surgeons because of several advantages, including minimal soft tissue requirements, low infection risk, and short consolidation time. However, in recent years, the application of the Masquelet technique has resulted in novel treatment methods for managing post-traumatic bone infections when bone defects are present. Although these new techniques do not constitute a panacea, they continue to be the most commonly employed options for treating complex large bone nonunion and bone defects. This review evaluates the currently available research on the Ilizarov and Masquelet bone transport techniques applied at various anatomical sites. Additionally, it explores treatment durations and associated complications to establish a theoretical foundation that can guide clinical treatment decisions and surgical procedures for the management of bone nonunion and bone defects.

HOXA11 promotes lymphatic metastasis of gastric cancer via transcriptional activation of TGFß1.

Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a key target, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFß1 expression and activates the TGFß1/Smad2 pathway, which not only promotes EMT development but also induces VEGF-C secretion and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor in lymphatic metastasis and suggest that HOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.

Age-Related Changes of the Zygomatic Ligament: An Experimental Animal Study.

BACKGROUND: Facial aging is a multifactorial process involving the skin, fat, muscles, bones, and ligaments. The role of facial ligaments in the facial aging process remains elusive. OBJECTIVES: The aim of this study was to identify whether age-related changes in facial ligaments exist and how to best quantify such changes when investigating the zygomatic ligament in the rat. METHODS: A total of 30 male Sprague-Dawley rats (10 young, 10 middle-aged, 10 mature) were investigated to visualize the zygomatic ligament. Samples of the ligaments spanning the zygomatic arch and the skin were taken and histologically examined with hematoxylin-eosin, Masson, Verhoeff's elastic, and picrosirius red staining. Quantification of the Type I/III collagen ratio and collagen content was performed by color deconvolution and electron microscopic imaging. RESULTS: With increasing age, collagen fibers inside of the examined ligaments appeared thicker and more closely arranged. The Type I/III collagen ratio was measured to be 1.74 in young animals, 3.93 in middle-aged animals, and 5.58 in mature animals. The ultra-microstructure of the ligament was less coordinated in direction and orientation in young and middle-aged animals than in mature animals, in which collagen fibers were bundled together in a strong and oriented mesh. CONCLUSIONS: Ligaments appeared thinner, transparent, more elastic, and less robust in young animals, whereas ligaments in mature animals appeared thicker, more fascia-like, less elastic, and more robust. An increase in the Type I/III collagen ratio, indicating greater stiffness and reduced elasticity, was observed with higher age of the investigated animals. These findings indicate that ligaments might increase in stiffness and rigidity with age.

Anti-tumor effect of Crocus sativus petals polysaccharides by reconstructing tumor microenvironment.

Two polysaccharides from Crocus sativus petals (PCSPs), PCSPA and PCSPB have been previously reported to possess the immunopotentiation activity and improve innate immunity in mice. In this study, PCSPB was evaluated for the anti-tumor activity and explored its immunological mechanisms based on tumor microenvironment (TME) using S180 sarcoma-bearing mice. Although PCSPB showed the lower toxicity to a series of tumor cells, it significantly and dose-dependently suppressed the growth of S180 sarcomas transplanted in mice. HE staining, immunohistochemical analysis, and TUNEL assay revealed that PCSPB significantly induced tumor cell necrosis, apoptosis, and vessel disruption in sarcoma tissues. Meanwhile, PCSPB markedly decreased the levels of inflammatory factors TGF-ß, IFN-γ, IL-10 and TNF-α and down-regulated the mRNA expression levels of TGF-ß and TNF-α in tumor tissues. Flow cytometric analysis showed that PCSPB significantly increased the proportion of CD8+ T cells and NK cells, but decreased that of regulatory T cells (Tregs), total myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) in sarcoma tissues. Furthermore, immunofluorescence assay demonstrated that PCSPB noteworthily reprogrammed TAMs from a tumorigenic M2 towards an antitumorigenic M1 phenotype in S180 tissues. These findings demonstrated that PCSPB might exert the anti-tumor activity by reconstructing TME and could act as an anti-tumor candidate with low toxicity.

Cancer Immunotherapy Based on Cell Membrane-Coated Nanocomposites Augmenting cGAS/STING Activation by Efferocytosis Blockade.

Innate immunity triggered by the cGAS/STING pathway has the potential to improve cancer immunotherapy. Previously, the authors reported that double-stranded DNA (dsDNA) released by dying tumor cells can trigger the cGAS/STING pathway. However, owing to efferocytosis, dying tumor cells are engulfed and cleared before the damaged dsDNA is released; hence, immunologic tolerance and immune escape occur. Herein, a cancer-cell-membrane biomimetic nanocomposites that exhibit tumor-immunotherapeutic effects are synthesized by augmenting the cGAS/STING pathway and suppressing efferocytosis. Once internalized by cancer cells, a combined chemo/chemodynamic therapy would be triggered, which damages their nuclear and mitochondrial DNA. Furthermore, the releasing Annexin A5 protein could inhibit efferocytosis effect and promote immunostimulatory secondary necrosis by preventing phosphatidylserine exposure, resulting in the burst release of dsDNA. These dsDNA fragments, as molecular patterns to immunogenic damage, escape from the cancer cells, activate the cGAS/STING pathway, enhance cross-presentation inside dendritic cells, and promote M1-polarization of tumor-associated macrophages. In vivo experiments suggest that the proposed nanocomposite could recruit cytotoxic T-cells and facilitate long-term immunological memory. Moreover, when combined with immune-checkpoint blockades, it could augment the immune response. Therefore, this novel biomimetic nanocomposite is a promising strategy for generating adaptive antitumor immune responses.

Aqueous-soluble components of sporoderm-removed Ganoderma lucidum spore powder promote ferroptosis in oral squamous cell carcinoma.

Objective: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment. However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of Ganoderma lucidum (G. lucidum) on oral squamous cell carcinoma (OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removed G. lucidum spore powder (A-GSP). Methods: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway. Cellular Fe2+, glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy (TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth. Results: A-GSP promoted ferroptosis in oral cancer cells by inducing Fe2+ influx, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acyl-coA synthetase long chain family member 4 (ACSL4) increase and glutathione peroxidase 4 (GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes. In vivo, A-GSP exerted a ferroptosis-mediated tumor-suppressing effect without observable adverse reactions. Conclusions: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis.

Dendrobium as a new natural source of bioactive for the prevention and treatment of digestive tract diseases: A comprehensive review with future perspectives.

BACKGROUND: The incidence of diseases related to the digestive tract is on the rise, with many types of complex etiologies. Dendrobium nobile Lindl. is a famous Traditional Chinese Medicine (TCM) rich in many bioactives proven to be beneficial in several health diseases related to inflammation and oxidative stress. PURPOSE: At present, despite the availability of various therapeutic clinical drugs used for the treatment of digestive tract diseases, resistance emergence and existence of several side effects warrant for the developing of novel drugs for improved effects on digestive tract diseases. METHODS: "Orchidaceae", "Dendrobium", "inflammation", "digestive tract", and "polysaccharide" were used as search terms to screen the literature. The therapeutic use of Dendrobium related to digestive tract diseases relative to known polysaccharides and other bioactive compounds were derived from online databases, including Web of Science, PubMed, Elsevier, Science Direct, and China National Knowledge Infrastructure, as well as relevant information on the known pharmacological actions of the listed phytochemicals. RESULTS: To better capitalize upon Dendrobium for preventing and treating diseases related to digestive tract, this review summarizes bioactives in Dendrobium reported of potential in digestive tract diseases management and their underlying action mechanisms. Studies revealed that Dendrobium encompasses diverse classes including polysaccharides, phenolics, alkaloids, bibenzyls, coumarins, phenanthrene and steroids, with polysaccharide as the major class. Dendrobium exerts various health effects on a variety of disease related to the digestive tract. Action mechanisms involve antioxidant, anti-inflammatory, anti-apoptotic, antioxidant, anticancer, alongside the regulation of some key signaling pathways. CONCLUSION: Overall, Dendrobium appears as a promising TCM source of bioactives that has the potential to be further developed into nutraceuticals for digestive tract diseases compared to current drug treatments. This review highlights for Dendrobium potential effects with future perspectives for needed future research to maximize the use of bioactive compounds from Dendrobium for digestive tract disease treatment. A compile of Dendrobium bioactives is also presented alongside methods for their extraction and enrichment for potential incorporation in nutraceuticals.