Myrtus communis leaves: source of bio - actives, traditional use, their biological properties, and prospects / Hojas de Myrtus communis: fuente de bioactivos, uso tradicional, sus propiedades biológicas y perspectivas

Myrtus communis L., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times, the inhabitant s of this area have been using it for its cultural and medicinal properties. Because of the vast diversity of biomolecules in its aerial parts, it exhibits several biological properties, including antioxidant, antimicrobial, and anticancer properties. This review retrospect the research on the source, biological activities with empirical evidence, chemical composition, applications, and cellular targets of extracts and essential oils obtained from M. communis leaves, which provides a perspective for further studies on the applications and formulations of extract and EO of M. communis leaves. The efficacy of constituents' individually, in association with other bioactive constituents, or in combination with available commercial drugs would provide insights in to the development of these bio - actives as future drugs and their evolving future potential applications in the pharmaceutical, food, and aroma industries.

Myrtus communis L., comúnmente conocido como arrayán verdadero, es una planta medicinal originaria de la zona mediterránea. Desde la antigüedad, los habitantes de esta zona lo utilizan por sus propiedades culturales y medicinales. Debido a la gran div ersidad de biomoléculas en sus partes aéreas, exhibe varias propiedades biológicas, incluidas propiedades antioxidantes, antimicrobianas y anticancerígenas. Esta revisión retrospectiva de la investigación sobre la fuente, las actividades biológicas con evi dencia empírica, la composición química, las aplicaciones y los objetivos celulares de los extractos y aceites esenciales obtenidos de las hojas de M. communis , lo que brinda una perspectiva para futuros estudios sobre las aplicaciones y formulaciones de l os extractos y EO de M. communis . La eficacia de los componentes individualmente, en asociación con otros componentes bioactivos o en combinación con medicamentos comerciales disponibles proporcionaría información sobre el desarrollo de estos bioactivos co mo medicamentos futuros y sus futuras aplicaciones potenciales en las industrias farmacéutica, alimentaria y aromática

Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Regulation of optimized new Shengmai powder on cardiomyocyte apoptosis and ferroptosis in ischemic heart failure rats: The mediating role of phosphatidylinositol-3-kinase/protein kinase B/tumor protein 53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.

Neutrophil-activating secretome characterizes palbociclib-induced senescence of breast cancer cells.

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation.

Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

Homogentisic acid metabolism inhibits papillary thyroid carcinoma proliferation through ROS and p21-induced cell cycle arrest.

Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.

Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Patients.

BACKGROUND Severe anemia caused by hemorrhoidal hematochezia is typically treated preoperatively with reference to severe anemia treatment strategies from other etiologies. This retrospective cohort study included 128 patients with hemorrhoidal severe anemia admitted to 3 hospitals from September 1, 2018, to August 1, 2023, and aimed to evaluate preoperative blood transfusion requirements. MATERIAL AND METHODS Of 5120 patients with hemorrhoids, 128 (2.25%; male/female: 72/56) experienced hemorrhoidal severe anemia, transfusion, and Milligan-Morgan surgery. Patients were categorized into 2 groups based on their preoperative hemoglobin (PHB) levels after transfusion: PHB ≥70 g/L as the liberal-transfusion group (LG), and PHB <70 as the restrictive-threshold group (RG). The general condition, bleeding duration, hemoglobin level on admission, transfusion volume, length of stay, immune transfusion reaction, surgical duration, and hospitalization cost were compared between the 2 groups. RESULTS Patients with severe anemia (age: 41.07±14.76) tended to be younger than those with common hemorrhoids (age: 49.431±15.59 years). The LG had a significantly higher transfusion volume (4.77±2.22 units), frequency of immune transfusion reactions (1.22±0.58), and hospitalization costs (16.69±3.31 thousand yuan) than the RG, which had a transfusion volume of 3.77±2.09 units, frequency of immune transfusion reactions of 0.44±0.51, and hospitalization costs of 15.00±3.06 thousand yuan. Surgical duration in the LG (25.69±14.71 min) was significantly lower than that of the RG (35.24±18.72 min). CONCLUSIONS Patients with hemorrhoids with severe anemia might require a lower preoperative transfusion threshold than the currently recognized threshold, with an undifferentiated treatment effect and additional benefits.

Physiological and Pathogenesis Significance of Chorein in Health and Disease.

This comprehensive review explores the physiological and pathophysiological significance of VPS13A, a protein encoded by the VPS13A gene. The VPS13A gene is associated with Chorea-acanthocytosis (ChAc), a rare hereditary neurodegenerative disorder. The review covers essential aspects, beginning with the genetics of VPS13A, highlighting its role in the pathogenesis of ChAc, and addressing the spectrum of genetic variants involved. It delves into the structure and function of the VPS13A protein, emphasizing its presence in various tissues and its potential involvement in protein trafficking and lipid homeostasis. Molecular functions of VPS13A in the brain tissue and other cell types or tissues with respect to their role in cytoskeletal regulation and autophagy are explored. Finally, it explores the intriguing link between VPS13A mutations, lipid imbalances, and neurodegeneration, shedding light on future research directions. Overall, this review serves as a comprehensive resource for understanding the pivotal role of VPS13A in health and disease, particularly in the context of ChAc. Key words: Chorein , Tumor, Actin, Microfilament, Gene expression, Chorea-acanthocytosis.

Netrin-1 Promotes M2 Type Activation and Inhibits Pyroptosis of Microglial Cells by Depressing RAC1/Nf-?B Pathway to Alleviate Inflammatory Pain.

Netrin-1 (NTN-1) plays a vital role in the progress of nervous system development and inflammatory diseases. However, the role and underlying mechanism of NTN-1 in inflammatory pain (IP) are unclear. BV2 microglia were treated with LPS to mimic the cell status under IP. Adeno-associated virus carrying the NTN-1 gene (AAV-NTN-1) was used to overexpress NTN-1. Complete Freund's Adjuvant (CFA)-induced mouse was recruited as an in vivo model. MTT and commercial kits were utilized to evaluate cell viability and cell death of BV2 cells. The mRNA expressions and secretions of cytokines were measured using the ELISA method. Also, the pyroptosis and activation of BV2 cells were investigated based on western blotting. To verify the role of Rac1/NF-kappaB signaling, isochamaejasmin (ISO) and AAV-Rac1 were presented. The results showed that NTN-1 expression was decreased in LPS-treated BV2 microglia and spinal cord tissues of CFA-injected mice. Overexpressing NTN-1 dramatically reversed cell viability and decreased cell death rate of BV2 microglia under lipopolysaccharide (LPS) stimulation, while the level of pyroptosis was inhibited. Besides, AAV-NTN-1 rescued the activation of microglia and inflammatory injury induced by LPS, decreasing IBA-1 expression, as well as iNOS, IL-1beta and IL-6 secretions. Meanwhile AAV-NTN-1 promoted the anti-inflammation response, including increases in Arg-1, IL-4 and IL-10 levels. In addition, the LPS-induced activation of Rac1/NF-kappaB signaling was depressed by NTN-1 overexpression. The same results were verified in a CFA-induced mouse model. In conclusion, NTN-1 alleviated IP by suppressing pyroptosis and promoting M2 type activation of microglia via inhibiting Rac1/NF-?B signaling, suggesting the protective role of NTN-1 in IP. Keywords: Netrin-1, Inflammatory pain, Pyroptosis, Microglia M2 activation, Rac1/NF-kappaB.

Electrical Stimulation-Based Twitch Exercise Suppresses Progression of Immobilization-Induced Muscle Fibrosis via Downregulation of PGC-1?/VEGF Pathway.

This study aimed to determine whether electrical stimulation-based twitch exercise is effective in inhibiting the progression of immobilization-induced muscle fibrosis. 19 Wistar rats were randomly divided into a control group (n=6), an immobilization group (n=6; with immobilization only), and a Belt group (n=7; with immobilization and twitch exercise through the belt electrode device, beginning 2 weeks after immobilization). The bilateral soleus muscles were harvested after the experimental period. The right soleus muscles were used for histological analysis, and the left soleus muscles were used for biochemical and molecular biological analysis. As a result, in the picrosirius red images, the perimysium and endomysium were thicker in both the immobilization and Belt groups compared to the control group. However, the perimysium and endomysium thickening were suppressed in the Belt group. The hydroxyproline content and alpha-SMA, TGF-beta1, and HIF-1alpha mRNA expressions were significantly higher in the immobilization and belt groups than in the control group. These expressions were significantly lower in the Belt group than in the immobilization group. The capillary-to-myofiber ratio and the mRNA expressions of VEGF and PGC-1alpha were significantly lower in the immobilization and belt groups than in the control group, these were significantly higher in the Belt group than in the immobilization group. From these results, Electrical stimulation-based twitch exercise using the belt electrode device may prevent the progression of immobilization-induced muscle fibrosis caused by downregulating PGC-1alpha/VEGF pathway, we surmised that this intervention strategy might be effective against the progression of muscle contracture. Keywords: Immobilization, Skeletal muscle, Fibrosis, Electrical stimulation-based twitch exercise, PGC-1alpha/VEGF pathway.

Protective Effects of Resveratrol Against Airway Hyperreactivity, Oxidative Stress, and Lung Inflammation in a Rat Pup Model of Bronchopulmonary Dysplasia.

Oxygen therapy provides an important treatment for preterm and low-birth-weight neonates, however, it has been shown that prolonged exposure to high levels of oxygen (hyperoxia) is one of the factors contributing to the development of bronchopulmonary dysplasia (BPD) by inducing lung injury and airway hyperreactivity. There is no effective therapy against the adverse effects of hyperoxia. Therefore, this study was undertaken to test the hypothesis that natural phytoalexin resveratrol will overcome hyperoxia-induced airway hyperreactivity, oxidative stress, and lung inflammation. Newborn rats were exposed to hyperoxia (fraction of inspired oxygen - FiO2>95 % O2) or ambient air (AA) for seven days. Resveratrol was supplemented either in vivo (30 mg·kg-1·day-1) by intraperitoneal administration or in vitro to the tracheal preparations in an organ bath (100 mikroM). Contractile and relaxant responses were studied in tracheal smooth muscle (TSM) using the in vitro organ bath system. To explain the involvement of nitric oxide in the mechanisms of the protective effect of resveratrol against hyperoxia, a nitric oxide synthase inhibitor - Nomega-nitro-L-arginine methyl ester (L-NAME), was administered in some sets of experiments. The superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and the tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels in the lungs were determined. Resveratrol significantly reduced contraction and restored the impaired relaxation of hyperoxia-exposed TSM (p<0.001). L-NAME reduced the inhibitory effect of resveratrol on TSM contractility, as well as its promotion relaxant effect (p<0.01). Resveratrol preserved the SOD and GPx activities and decreased the expression of TNF-alpha and IL-1beta in hyperoxic animals. The findings of this study demonstrate the protective effect of resveratrol against hyperoxia-induced airway hyperreactivity and lung damage and suggest that resveratrol might serve as a therapy to prevent the adverse effects of neonatal hyperoxia. Keywords: Bronchopulmonary dysplasia, Hyperoxia, Airway hyperreactivity, Resveratrol, Pro-inflammatory cytokines.

The Salutary Effects of Diminazene, Lisinopril or Valsartan on Cisplatin - Induced Acute Kidney Injury in Rats: A Comparative Study.

Nephrotoxicity as a cause of acute kidney injury (AKI) induced by cisplatin (CP), limits its usefulness as an anticancer agent. Diminazene, an angiotensin converting enzyme 2 activator, exhibited renoprotective properties on rat models of kidney diseases. This research aims to investigate the salutary effect of diminazene in comparison with lisinopril or valsartan in CP-induced AKI. The first and second groups of rats received oral vehicle (distilled water) for 9 days, and saline injection or intraperitoneal CP (6 mg/kg) on day 6, respectively. Third, fourth, and fifth groups received intraperitoneal injections of CP on day 6 and diminazene (15 mg/kg/day, orally), lisinopril (10 mg/kg/day, orally), or valsartan (30 mg/kg/day, orally), for 9 days, respectively. 24h after the last day of treatment, blood and kidneys were removed under anesthesia for biochemical and histopathological examination. Urine during the last 24 h before sacrificing the rats was also collected. CP significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin, calcium, phosphorus, and uric acid. It also increased urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase/creatinine ratio, and reduced creatinine clearance, as well the plasma concentrations of inflammatory cytokines [plasma tumor necrosis factor-alpha, and interleukin-1beta], and significantly reduced antioxidant indices [catalase, glutathione reductase , and superoxide dismutase]. Histopathologically, CP treatment caused necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. Diminazine, lisinopril, and valsartan ameliorated CP-induced biochemical and histopathological changes to a similar extent. The salutary effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Keywords: Cisplatin, Diminazene, ACE2 activator, Lisinopril, Valsartan, Acute kidney injury.

Revealing the potential of solute carrier family 31 (copper transporters), member 1: Insights into its role in bladder cancer progression and therapeutic implications.

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.

Uncovering novel therapeutic targets in glucose, nucleotides and lipids metabolism during cancer and neurological diseases.

BACKGROUND: Cell metabolism functions without a stop in normal and pathological cells. Different metabolic changes occur in the disease. Cell metabolism influences biochemical and metabolic processes, signaling pathways, and gene regulation. Knowledge regarding disease metabolism is limited. OBJECTIVE: The review examines the cell metabolism of glucose, nucleotides, and lipids during homeostatic and pathological conditions of neurotoxicity, neuroimmunological disease, Parkinson's disease, thymoma in myasthenia gravis, and colorectal cancer. METHODS: Data collection includes electronic databases, the National Center for Biotechnology Information, and Google Scholar, with several inclusion criteria: cell metabolism, glucose metabolism, nucleotide metabolism, and lipid metabolism in health and disease patients suffering from neurotoxicity, neuroinflammation, Parkinson's disease, thymoma in myasthenia gravis. The initial number of collected and analyzed papers is 250. The final analysis included 150 studies out of 94 selected papers. After the selection process, 62.67% remains useful. RESULTS AND CONCLUSION: A literature search shows that signaling molecules are involved in metabolic changes in cells. Differences between cancer and neuroimmunological diseases are present in the result section. Our finding enables insight into novel therapeutic targets and the development of scientific approaches for cancer and neurological disease onset, outcome, progression, and treatment, highlighting the importance of metabolic dysregulation. Current understanding, emerging research technologies and potential therapeutic interventions in metabolic programming is disucussed and highlighted.

Establishment of Induced Pancreatic Stem Cells by Yes-Associated Protein 1.

Recently, we and others generated induced tissue-specific stem/progenitor (iTS/iTP) cells. The advantages of iTS/iTP cells compared with induced pluripotent stem (iPS) cells are (1) easier generation, (2) efficient differentiation, and (3) no teratomas formation. In this study, we generated mouse induced pancreatic stem cells (iTS-P cells) by the plasmid vector expressing Yes-associated protein 1 (YAP). The iTS-P YAP9 cells expressed Foxa2 (endoderm marker) and Pdx1 (pancreatic marker) while the expressions of Oct3/4 and Nanog (marker of embryonic stem [ES] cells) in iTS-P YAP9 cells was significantly lower compared with those in ES cells. The iTS-P YAP9 cells efficiently differentiated into insulin-expressing cells compared with ES cells. The ability to generate autologous iTS cells may be applied to diverse applications of regenerative medicine.

Potential Application of Modified mRNA in Cardiac Regeneration.

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma.

BACKGROUND: Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. METHODS: We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. RESULTS: The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). CONCLUSION: Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

BackgroundLiquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.MethodsWe retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.ResultsThe positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001).ConclusionOur findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

B cells in the pneumococcus-infected lung are heterogeneous and require CD4+ T cell help including CD40L to become resident memory B cells.

Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (BRM) cells. The B cells in the early wave were activated, proliferating locally, and associated with both CD4+ T cells and CXCL13. Antagonist- and antibody-mediated interventions were implemented during this early timeframe to demonstrate that lymphocyte recirculation, CD4+ cells, and CD40 ligand (CD40L) signaling were all needed for lung BRM cell establishment, whereas CXCL13 signaling was not. While most prominent as aggregates in the loose connective tissue of bronchovascular bundles, morphometry and live lung imaging analyses showed that lung BRM cells were equally numerous as single cells dispersed throughout the alveolar septae. We propose that CD40L signaling from antigen-stimulated CD4+ T cells in the infected lung is critical to establishment of local BRM cells, which subsequently protect the airways and parenchyma against future potential infections.

Dose-dependent multi-organ injury following lipopolysaccharide gas inhalation.

Lipopolysaccharide (LPS) is widely used to establish various animal models, including models of acute lung injury, cardiomyocyte damage, and acute kidney injury. Currently, there is no consensus on the diagnosis and treatment of LPS-induced disease. We herein present a case series of four patients who developed dose-dependent multi-organ injury, including acute lung injury and acute kidney injury, after inhaling LPS gas in a sealed room. These patients exhibited varying degrees of multi-organ injury characterized by inflammatory cell infiltration and secretion of proinflammatory cytokines. One patient showed progressive symptoms even with active treatment, leading to mild pulmonary fibrosis. This study emphasizes the importance of early diagnosis and treatment of significant LPS exposure and suggests personalized treatment approaches for managing LPS poisoning.