Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and ...hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey’s multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.
•An immune-modulator was prepared by concentrating cytokines and growth factors in urine.•It can boost immunomodulatory responses in allergic and autoimmune disease patients.•The immune-modulator is ...administrated sublingually.•This strategy aims to boost the immunomodulatory response of the treated patients.
At “Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C.” in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an “immune-modulator” has been developed. In this study, we will refer to this treatment substance as the “immune-modulator.” In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator.
Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay.
Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1β, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65–70% of samples; IL5, IL-1B, and IL-17 in 50–60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20–30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1β, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment.
The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.
Malva parviflora has shown anti-inflammatory, antihypertensive, antihyperlipidemic, and hypoglycemic effects. This study is aimed to evaluate the anti-adipogenic effect of M. parviflora on 3T3-L1 ...adipocytes. Fibroblast differentiation was induced either in the absence or presence of M. parviflora fractions (F3, F4, F7, F12, F13, F17, F18 and F19) for 4 days; F17 and 18 were the most effective fractions in reducing intracellular lipid accumulation (by 25.6% and 23.1%, respectively). EC50 of F17 and F18 (14 μg/mL and 17 μg/mL, respectively) were used to evaluate their anti adipogenic effect. After 10 days of inducing differentiation in the absence or presence of the extracts at the EC50 of F17 and F18, lipid accumulation, the concentration of interleukin 6 (IL-6) were measured in the culture medium; the presence of PPAR-γ, AKT, and p-AKT was also determined. In differentiated adipocytes (C2), F17 maintained intracellular lipid concentration at levels comparable to metformin, while decreasing PPAR-γ and increasing p-AKT presence; it also prevented IL-6 expression. F17 consists of alanine, valine, phenylalanine, and proline. On the other hand, F18 reduced intracellular lipid concentrations, prevented the increase of PPAR-γ and p-AKT, and maintained IL-6 expression at similar levels as metformin. F18 is mainly constituted by alanine, valine, proline, and sucrose. In conclusion, M. parviflora fractions (F17 and F18) control the process of adipogenesis, lipogenesis, and cellular dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
4.
The role of gastrointestinal endoscopy in Kaposi sarcoma Gonzalez-Ballesteros, Patricia; de la Mora Levy, José Guillermo; Amaya-Fragoso, Edgardo ...
Revista española de enfermedades digestivas,
12/2023, Letnik:
115, Številka:
12
Journal Article
Recenzirano
Odprti dostop
We are writing to make endoscopists aware of the paramount of a prompt diagnosis of gastrointestinal Kaposi sarcoma (GI-KS). Patients with GI involvement have a two to five times higher risk of death ...and will benefit from chemotherapy to improve their survival. However, current evidence found that one out of three patients might have a false negative result even with HHV-8 since other entities such as gastrointestinal stromal tumors, angiosarcoma, and lymphoma shared macroscopic and histopathological characteristics. These cause a delay in treatment and significantly worsen the prognosis. We observed a trend for a positive diagnosis from ulcers and nodules. To our knowledge, this is the largest cohort of patients with GI-KS in the world. Our study suggests that in cases where a complete immunochemistry panel for KS is not available, HHV-8 remains as a bare minimum. However, other gastrointestinal lesions shared histopathological characteristics. Therefore, we suggest taking biopsies from nodular and ulcer-type lesions to increase the probability to establish a histopathological diagnosis.
MicroRNAs are small noncoding transcripts that posttranscriptionally regulate gene expression via base-pairing complementarity. Their role in cancer can be related to tumor suppression or oncogenic ...function. Moreover, they have been linked to processes recognized as hallmarks of cancer, such as apoptosis, invasion, metastasis, and proliferation. Particularly, one of the first oncomiRs found upregulated in a variety of cancers, such as gliomas, breast cancer, and colorectal cancer, was microRNA-21 (miR-21). Some of its target genes associated with cancer are PTEN (phosphatase and tensin homolog), PDCD4 (programmed cell death protein 4), RECK (reversion-inducing cysteine-rich protein with Kazal motifs), and STAT3 (signal transducer activator of transcription 3). As a result, miR-21 has been proposed as a plausible diagnostic and prognostic biomarker, as well as a therapeutic target for several types of cancer. Currently, research and clinical trials to inhibit miR-21 through anti-miR-21 oligonucleotides and ADM-21 are being conducted. As all of the evidence suggests, miR-21 is involved in carcinogenic processes; therefore, inhibiting it could have effects on more than one type of cancer. However, whether miR-21 can be used as a tissue-specific biomarker should be analyzed with caution. Consequently, the purpose of this review is to outline the available information and recent advances regarding miR-21 as a potential biomarker in the clinical setting and as a therapeutic target in cancer to highlight its importance in the era of precision medicine.
We identified the main changes in serum metabolites associated with severe (n = 46) and mild (n = 19) COVID-19 patients by gas chromatography coupled to mass spectrometry. The modified metabolic ...profiles were associated to an altered amino acid catabolism in hypoxic conditions. Noteworthy, three α-hydroxyl acids of amino acid origin increased with disease severity and correlated with altered oxygen saturation levels and clinical markers of lung damage. We hypothesize that the enzymatic conversion of α-keto-acids to α- hydroxyl-acids helps to maintain NAD recycling in patients with altered oxygen levels, highlighting the potential relevance of amino acid supplementation during SARS-CoV-2 infection.
SARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully ...elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.
Using a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.
The frequency of CD19
B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.
The severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.
Here, economic losses caused by cattle parasites in Mexico were estimated on an annual basis. The main factors taken into consideration for this assessment included the total number of animals at ...risk, potential detrimental effects of parasitism on milk production or weight gain, and records of condemnation on livestock byproducts. Estimates in US dollars (US$) were based on reported yield losses in untreated animals. These estimates reflect the major effects on cattle productivity of six parasites, or parasite group. The potential economic impact (US$ millions) was: gastrointestinal nematodes US$ 445.10; coccidia (Eimeria spp.) US$ 23.78; liver fluke (Fasciola hepatica) US$ 130.91; cattle tick (Rhipicephalus microplus) US$ 573.61; horn fly (Haematobia irritans) US$ 231.67; and stable fly (Stomoxys calcitrans) US$ 6.79. Overall, the yearly economic loss due to the six major parasites of cattle in Mexico was estimated to be US$ 1.41 billion. Considering that the national cattle herd registered in 2013 included 32.40 million head, the estimated yearly loss per head was US$ 43.57. The limitations of some of the baseline studies used to develop these estimates, particularly when extrapolated from local situations to a national scale, are acknowledged. However, the general picture obtained from the present effort demonstrates the magnitude and importance of cattle parasitism in Mexico and the challenges to maximize profitability by the livestock industry without adapting sustainable and integrated parasite control strategies.
Here, economic losses caused by cattle parasites in Mexico were estimated on an annual basis. The main factors taken into consideration for this assessment included the total number of animals at risk, potential detrimental effects of parasitism on milk production or weight gain, and records of condemnation on livestock byproducts. Estimates in US dollars (US$) were based on reported yield losses in untreated animals. These estimates reflect the major effects on cattle productivity of six parasites, or parasite group. The potential economic impact (US$ millions) was: gastrointestinal nematodes US$ 445.10; coccidia (Eimeria spp.) US$ 23.78; liver fluke (Fasciola hepatica) US$ 130.91; cattle tick (Rhipicephalus microplus) US$ 573.61; horn fly (Haematobia irritans) US$ 231.67; and stable fly (Stomoxys calcitrans) US$ 6.79. Overall, the yearly economic loss due to the six major parasites of cattle in Mexico was estimated to be US$ 1.41 billion. Considering that the national cattle herd registered in 2013 included 32.40 million head, the estimated yearly loss per head was US$ 43.57. The limitations of some of the baseline studies used to develop these estimates, particularly when extrapolated from local situations to a national scale, are acknowledged. However, the general picture obtained from the present effort demonstrates the magnitude and importance of cattle parasitism in Mexico and the challenges to maximize profitability by the livestock industry without adapting sustainable and integrated parasite control strategies.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes de COVID-19 disease use as a principal receptor the angiotensin-converting enzyme-2 (ACE2). It has been ...suggested that dipeptidyl peptidase-4 (DPP4) can be another possible receptor for this virus. The present study aimed to establish if the DPP4 levels and DPP4 polymorphisms are associated with COVID-19 disease and its severity.
The study included 107 COVID-19 patients and 263 matched-healthy controls. Fifty patients required invasive mechanical ventilation. The DPP4 was quantified in serum using the Bioplex system. Based on the previous results and the functional prediction analysis, we select for the study 5 DPP4 polymorphisms (rs12617336, rs12617656, rs1558957, rs3788979, and rs17574) and these were determined using the 5´exonuclease TaqMan assays.
Low levels of DPP4 were observed in COVID-19 patients (46.5 33.1–57.7 ng/mL) when compared to healthy controls (125.3 100.3–157.3 ng/mL) (P < 0.0001). Also, patients that required mechanical ventilation showed lower DPP4 levels (42.8 29.8–56.9 ng/mL) than those that did not need this procedure (49.2 39.9–65.6 ng/mL) (P = 0.012). DPP4 levels correlated negatively with age, fibrinogen, and platelet levels, and positively with albumin, alanine aminotransferase, and percentage of neutrophils. The DPP4 rs3788979 polymorphism was associated with a high risk of COVID-19 disease and, the TT genotype carriers had the lowest DPP4 levels.
In summary, in the present study, an association of low levels of DPP4 with COVID-19 disease and severity was found. The association of the DPP4 rs3788979 polymorphism with COVID-19 is also reported.
AbstractLiver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibro-sis, viral infection is most common (hepatitis B and ...C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.
PDF
