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Mashup Score: 4Antiviral therapy for chronic hepatitis delta: new insights from clinical trials and real-life studies - 6 day(s) ago
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, carrying a greater risk of developing cirrhosis and its complications. For decades, pegylated interferon alpha (PegIFN-α) has represented the only therapeutic option, with limited virological response rates and poor tolerability. In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis. Long-term BLV monotherapy may reduce decompensating events in patients with cirrhosis. The combination of BLV 2 mg with PegIFN-α increased the HDV RNA undetectability rates on-therapy but not off-therapy, compared with PegIFN monotherapy. However, combination therapy, but not BLV monotherapy, may induce hepatitis B surface antigen (HBsAg) loss in some patients. The PegIFN lambda study has be
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet
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Mashup Score: 12
Background GI cancers pose an increasing global health burden, with their impact on the working-age population (WAP) aged 15–64 years remaining largely unexplored despite the crucial role of this group in societal and economic well-being. Objective To assess trends and cross-country inequality in the global burden of six GI cancers from 1990 to 2021 among individuals in the WAP. Design The 2021 Global Burden of Disease study dataset was used to obtain estimates of GI cancer incidence and 95% uncertainty intervals, including the number of cases, crude incidence rate and age-standardised incidence rate (ASIR). WAP GI cancer epidemiology was assessed at the national, regional and global levels, evaluating trends from 1990 to 2021 from overall, local and Sociodemographic Index (SDI) perspectives and using standard health equity methods to quantify cross-country inequality. Results Colorectal cancer exhibited the greatest burden of GI cancer among the WAP in 2021. From 1990 to 2021, the num
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTOnline paper by Song et al entitled "Trends and cross-country inequality in the incidence of GI cancers among the working-age population from 1990 to 2021: a Global Burden of Disease 2021 analysis" via https://t.co/rQzQDt716U #GICancers https://t.co/Miyro2IVtD
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Mashup Score: 6Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis - 6 day(s) ago
Objective The specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. Design We enrolled 250 mother–infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings. Results The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacte
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Jiang et al entitled "Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis" via https://t.co/IScAQ67MlG #Dysbiosis #Microbiome https://t.co/anPvpiqSAP
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Mashup Score: 10
Background Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified. Objective We characterised the enzyme protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in CCA. Design We evaluated the expression of PRMT5, its functional partner MEP50 and methylthioadenosine phosphorylase (MTAP)—an enzyme that modulates the sensitivity of PRMT5 to pharmacological inhibitors—in human CCA tissues. PRMT5-targeting drugs, currently tested in clinical trials for other malignancies, were assessed in human CCA cell lines and organoids, as well as in two immunocompetent CCA mouse models. Transcriptomic, proteomic and functional analyses were performed to explore the underlying antitumoural mechanisms. Results PRMT5 and MEP50 proteins were correlatively overexpressed in most CCA tissues. MTAP was absent in 25% of intrahepatic C
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Elurbide et al entitled "Identification of PRMT5 as a therapeutic target in cholangiocarcinoma" via https://t.co/gX3fKt3HXz @Areche_M @chantar_m @CUBEROlab @MaiteGF_B #Cholangiocarcinoma https://t.co/KVROdF3kOn
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Mashup Score: 16Detection of large flat colorectal lesions by artificial intelligence: a persistent weakness and blind spot - 7 day(s) ago
Computer-aided detection (CADe) has increased adenoma detection in randomised trials. However, unlike other detection adjuncts, CADe is lesion specific, that is, it is trained on a specific set of lesions. If the training does not include sufficient examples of precancerous lesion subsets, CADe may not perform adequately for lesions in that subset. In a prospective assessment of a second-generation CADe programme in 165 colonoscopies, we identified 26 flat lesions ≥10 mm in 17 patients. The endoscopist identified 22 of 26 lesions before the CADe programme. In 13 lesions, the CADe either generated no detection signal or only a signal over part of the lesion after colonoscope position or luminal inflation adjustment. Thus, the second-generation CADe algorithm, like the first generation, frequently fails to effectively detect large flat colorectal lesions, which are likely very important lesions that a CADe programme should identify. The first CADe programme to be launched commercially in
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#EndoscopyNews paper by @Rex_colonoscopy et al on "Detection of large flat colorectal lesions by artificial intelligence: a persistent weakness and blind spot" via https://t.co/sCwdmL8OXO @JohnGuardiolaMD #AI https://t.co/xlWD38wOOw
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Mashup Score: 19Immune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events - 7 day(s) ago
Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards of care and increasing patient survival. In both liver tumour types, which commonly arise in the context of liver inflammation and underlying functional impairment, the lack of validated predictors of response underscores the need to balance predicted gains in survival with risk of treatment-related hepatoxicity and decompensation of underlying chronic liver disease. In addition, the liver is implicated in the toxicity associated with ICI therapy for non-liver cancers, which exhibits a high degree of variability in presentation and severity. An accurate assessment is mandatory for the diagnosis and management of ICI-induced liver injury. In this Recent Advances article, we provide an overview of the mechanisms of efficacy and toxicity of anticancer immunotherapy in liver tumours and liver toxici
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTOnline #RecentAdvancesInBasicScience paper by De Martin et al on "Immune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events" via https://t.co/pMsf6eN2Bx #ICI #Liver https://t.co/2HpLt572SD
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Mashup Score: 17Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet? - 7 day(s) ago
Despite significant advances in biologic and small molecule treatments and the emergence of combination therapies to treat inflammatory bowel diseases (IBD) a large unmet need remains to control intestinal inflammation. New approaches targeting several pathways simultaneously with a favorable safety profile and agents that trigger anti-inflammatory pathways to drive durable resolution of inflammation are needed. This article discusses novel cellular immunotherapies and immune cell depleting therapies in IBD, including CAR-T cell approaches, Tr1 and T regulatory (Treg) cells and cell depleting antibodies such as rosnilimab. These novel approaches have the potential to overcome current therapeutic limitations in the treatment of IBD.
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the #GUTLeadingArticle by Neurath et al entitled "Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet?" via https://t.co/IWZEULMMLG @IBD_FloMD #IBD https://t.co/eKwotSptTs
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Mashup Score: 33Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma - 7 day(s) ago
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community. Host genetics influence the composition of gut microbiome, while the gut microbiota and their derived metabolites can induce host epigenetic modifications to affect the development of MASLD. The exploration of the intricate relationship between the gut microbiome and the genetic/epigenetic makeup of the host is anticipated to yield promising avenues for therapeutic interventions targeting MASLD and its associated conditions. In this review, we summarise the effects of gut microbiome, host genetics and epigenetic alterations in MASLD and MASLD-HCC. We further discuss research findings demon
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the #RecentAdvancesInBasicScience paper by Ha et al entitled "Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma" via https://t.co/QyMWBSWoXq #MASLD #HCC https://t.co/7AjoAEYQkq
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Mashup Score: 4Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC - 8 day(s) ago
Background The potency of T cell-mediated responses is a determinant of immunotherapy effectiveness in treating malignancies; however, the clinical efficacy of T-cell therapies has been limited in hepatocellular carcinoma (HCC) owing to the extensive immunosuppressive microenvironment. Objective Here, we aimed to investigate the key genes contributing to immune escape in HCC and raise a new therapeutic strategy for remoulding the HCC microenvironment. Design The genome-wide in vivo clustered regularly interspaced short palindromic repeats (CRISPR) screen library was conducted to identify the key genes associated with immune tolerance. Single-cell RNA-seq (scRNA-seq), flow cytometry, HCC mouse models, chromatin immunoprecipitation and coimmunoprecipitation were used to explore the function and mechanism of adenylate cyclase 7 (ADCY7) in HCC immune surveillance. Results Here, a genome-wide in vivo CRISPR screen identified a novel immune modulator-ADCY7. The transmembrane protein ADCY7 un
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Chen et al entitled "Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC" via https://t.co/kzApSM9RJ9 #HCC https://t.co/6HuPG2ezWO
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Mashup Score: 8Targeting the oncogenic m6A demethylase FTO suppresses tumourigenesis and potentiates immune response in hepatocellular carcinoma - 8 day(s) ago
Objective Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown. Design The functions and mechanisms of FTO and glycoprotein non-metastatic melanoma protein B (GPNMB) in HCC progression were investigated in vitro and in vivo. Neutralising antibody of syndecan-4 (SDC4) was used to assess the significance of sEV-GPNMB. FTO inhibitor CS2 was used to examine the effects on anti-PD-1 and sorafenib treatment. Results FTO expression was upregulated in patient HCC tumours. Functionally, FTO promoted HCC cell proliferation, migration and invasion in vitro, and tumour growth and metastasis in vivo. FTO knockdown enhanced the activation and recruitment of tumo
Source: gut.bmj.comCategories: General Medicine News, GastroenterologyTweet-
#GUTImage from the paper by Chen et al entitled "Targeting the oncogenic m6A demethylase FTO suppresses tumourigenesis and potentiates immune response in hepatocellular carcinoma" https://t.co/YWmo7PUKBX #HCC https://t.co/q1rQP82Pr9
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#GUTOnline #RecentAdvancesInClinicalPractice paper by Pietro Lampertico et al on "Antiviral therapy for chronic hepatitis delta: new insights from clinical trials and real-life studies" via https://t.co/7vBgdJzSgA @NO_hep @Hep_Alliance @HepBFoundation #HDV #HBV https://t.co/cJQCLIp38R