Therapeutic Effects of Combining Curcumin and Swimming in Osteoarthritis Using a Rat Model

Osteoarthritis (OA) is a common debilitating degenerative disease of the elderly. We aimed to study the therapeutic effects of combining curcumin and swimming in monosodium iodoacetate (MIA)-induced OA in a rat model. The rats were divided into 5 groups (n = 9). Group 1 received saline and served as a control group. Groups 2-5 were injected intra-articularly in the right knee with 100 μL MIA. One week later, groups 3 and 5 were started on daily swimming sessions that gradually increased to 20-mins per session, and for groups 4 and 5, oral curcumin was administered at a dose of 200 mg/kg for 4 weeks. The combination therapy (curcumin + swimming) showed the most effective results in alleviating pain and joint stiffness as well as improving histological and radiological osteoarthritis manifestations in the knee joints. The combination modality also reduced serum C-reactive protein and tissue cartilage oligomeric matrix protein levels. Mechanistically, rats received dual treatment exhibited restoration of miR-130a and HDAC3 expression. The dual treatment also upregulated PPAR-γ alongside downregulation of NF-κB and its inflammatory cytokine targets TNF-α and IL-1β. Additionally, there was downregulation of MMP1 and MMP13 in the treated rats. In conclusion, our data showed that there is a therapeutic potential for combining curcumin with swimming in OA, which is attributed, at least in part, to the modulation of miR-130a/HDAC3/PPAR-γ signaling axis

Efectividad de la mezcla Fluopyram + Tebuconazole en el control de Alternaria solani en papas

27 p.La papa (Solanum tuberosum L.), como todo cultivo, esta afecto a diversas plagas y enfermedades que lo pueden atacar y disminuir sus rendimientos sustancialmente, por lo que ha sido tema obligado de variadas investigaciones. Dentro de las enfermedades, las más importantes que afectan al cultivo de la papa son Tizón Tardío causado por el hongo Phytophthora infestans y Tizón Temprano ocasionado por el hongo Alternaria solani. Específicamente, el Tizón Temprano de la papa, ataca follaje y tubérculos de la planta, provocando pérdidas en rendimiento que van desde 10% a 50% dependiendo del grado de infección del hongo sobre la planta.Para el control de la enfermedad se han sugerido diversas prácticas culturales, como por ejemplo la utilización de semilla de buena calidad. Paralelamente, el control químico se ha presentado como una alternativa eficiente en el control de la enfermedad.Debido a lo anterior se realizó un ensayo con el objetivo de evaluar la efectividad de la mezcla Fluopyram y Tebuconazole en el control de la enfermedad tizón temprano causado por el hongo Alternaria solani en un cultivo de papas. Se evaluaron diferentes dosis de la mezcla incluyendo una que agregaba un surfactante. Estas mezclas fueron comparadas con un tratamiento testigo y con fungicidas de uso tradicional que tienen como ingrediente activo a Boscalid, Trifloxystrobin, Cyproconazole o Difenoconazole. Los tratamientos se distribuyeron en un diseño de bloques completamente al azar y fueron aplicados durante tres ocasiones: fin de floración, 10 días después de floración y 20 días después de floración. Para medir el efecto de cada uno de los tratamientos se hicieron dos evaluaciones de incidencia y severidad y una evaluación de rendimiento. Los resultados obtenidos a partir de este ensayo demostraron la efectividad de cada uno de los fungicidas sobre la disminución en la incidencia y severidad del ataque del hongo A. solani. Sin embargo no se observaron diferencias estadísticamente significativas entre las mezclas de Fluopyram + Tebuconazole y los fungicidas de uso comercial. En el caso de la evaluación de rendimiento, no se observaron diferencias estadísticamente significativas entre los tratamientos. Palabras clave: Papa; Solanum Tuberosum L; Tizón Temprano; Alternaria solani; Fluopyram; Tebuconazole./ABSTRACT: Potato (Solanum tuberosum L.), like any crop it is affected for many pests and diseases which can decrease yields, turning these problems in to an important research topic. Within, the most important diseases that affect potato we can mention late blight caused by the fungus Phytophthora infestans and early blight produced by the fungus Alternaria solani. Specifically, early blight, affects foliage and tubers of the plant, causing yield losses ranging from 10% to 50% depending on the degree of infection. To control of the disease includes various cultural practices such as the use of good quality seed. In parallel, chemical control has resulted an efficient alternative in the control of the disease. The purpose of this assay it was to evaluate the effectiveness of the active ingredients Fluopyram and Tebuconazole in mixture in the control of early blight caused by the fungus Alternaria solani in a potato. Different doses of the mixture were incorporated in the experiment as treatments, including the addition of a surfactant. These were compared with a control treatment and with fungicides traditionally used such as Boscalid, Trifloxystrobin, Cyproconazole or Difenoconazole. The treatments were distributed in a completely randomized blocks experimental design, being applied three times: at the end of flowering, 10 days after flowering and 20 days after flowering. To measure the effect of each treatment two evaluations of incidence and severity were made. The yield at harvest was also measured. The results of this experiment demonstrated the effectiveness of each of the fungicides evaluated in the reduction of the incidence and severity of the disease. However, no statistically significant differences between the mixtures fluopyram + Tebuconazole and the commercial fungicides were observed. For yield evaluation, no statistically significant differences between treatments were observed. Keywords: Potato; Solanum tuberosum L; Early blight; Alternaria solani; Fluopyram; Tebuconazole

Plasma Growth Hormone as a Prognostic Biomarker to Durvalumab and Tremelimumab in Patients with Advanced Hepatocellular Carcinoma

INTRODUCTION: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T). METHODS: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 μg/L and ≤0.9 μg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups. RESULTS: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036). CONCLUSION: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients

Severe Febrile Neutropenia and Pancytopenia in a Patient With Advanced Hepatocellular Carcinoma Treated With Atezolizumab and Bevacizumab: A Case Report

BACKGROUND: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course. CASE DESCRIPTION: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a fever of 39.0 ℃ 10 days after therapy initiation. He presented 5 days later with persistent fever as well as a headache, vomiting, chills, generalized pain, fatigue, mild abdominal discomfort, and a burning rash present on his neck and face. Complete blood counts showed severe neutropenia [absolute neutrophil count (ANC) of 90 cells/µL], leukopenia [white blood cell (WBC) count 500 cells/µL], thrombocytopenia [platelet count (PC) 18,000 cells/µL], and mild anemia (hemoglobin level 12.6 gm/dL). Imaging findings showed colitis on computed tomography (CT). Atezo/bev therapy was discontinued. Treatment plan constituted of cefepime and filgrastim, a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia, metronidazole for colitis, and intravenous methylprednisolone for immune-related toxicities. The patient fully recovered after 4 days of admission. CONCLUSIONS: In conclusion, we observed temporary severe febrile neutropenia and pancytopenia during systemic immunotherapy in a patient with unresectable HCC. Healthcare providers should consider hematological irAEs (hem-irAEs) in patients after the administration of ICIs

Plasma Growth Hormone is a Potential Biomarker of Response to Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma Patients

INTRODUCTION: Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev). MATERIALS AND METHODS: Study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 μg/L and ≤0.9 μg/L, respectively). Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups. RESULTS: Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37-80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; DISCUSSION AND CONCLUSIONS: Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients

Evaluation of In Vitro Antioxidant, Anti-Obesity, and Anti-Diabetic Activities of

Opuntia ficus cladodes (OFC) are considered one of the wastes that result from opuntia cultivation, and their disposal by traditional methods results in many environmental problems. Therefore, this study was conducted with two aims. The first was the production of OFC gel, and the evaluation of its in vitro antioxidant (by two methods, DPPH and ABTS), anti-obesity, and anti-diabetic activities. The second was an investigation of the effects of different concentrations of this gel (0, 50, and 100%) as an edible coating on the quality of shrimp during 8 days of refrigerated storage. The results showed that this gel was characterised by a high content of ash (10.42%), total carbohydrates (75.17%), and total phenols (19.79 mg GAE/g). OFC gel contained six types of sugars: arabinose, xylose, galactose, rhamnose, glucose, and uronic acid, and the most abundant was xylose (36.72%). It is also clear from the results that the OFC gel had high antioxidant properties, which were higher against DPPH than ABTS at the same concentration. OFC gel showed a high inhibition activity against lipase, α-glycosidase, and α-amylase enzymes, and their IC50 values were 1.43 mg/mL, 0.78 mg/mL, and 0.57 mg/mL, respectively. The results also stated that shrimp coated with OFC gel had lower pH, drip loss, TVB-N, and TBA values through the days of refrigerated storage. Moreover, the shrimp coated with 100% OFC gel were better than those coated with 50% OFC gel. In conclusion, OFC gel showed high potency as active antioxidant, for its enzyme anti-activities, and as an edible coating for shrimp

The Gut Microbiome as a Biomarker and Therapeutic Target in Hepatocellular Carcinoma

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome\u27s role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy

The Gut Microbiome as a Biomarker and Therapeutic Target in Hepatocellular Carcinoma

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome\u27s role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy

Clinical and Prognostic Biomarker Value of Blood-Circulating Inflammatory Cytokines in Hepatocellular Carcinoma

INTRODUCTION: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data have suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs is yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. METHODS: We prospectively collected data and serum samples from 767 HCC patients treated at the University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% confidence interval [CI]: 52.5, 83.3). Biomarker association with OS was evaluated by the log-rank method. RESULTS: The median OS in this cohort was 14.2 months (95% CI: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. CONCLUSION: Our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC

Metabolic response to subacute and subchronic iron overload in a rat model

One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg−1) and subchronic (0.1 mg kg−1) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L−1 and 13.2 μmol g−1 wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities “TIBC, UIBC” as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system