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Hepatology Communications Jul 2024The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
BACKGROUND
The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.
METHODS
Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).
RESULTS
Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.
CONCLUSIONS
We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.
Topics: Animals; Myosin-Light-Chain Phosphatase; Mice; Disease Models, Animal; Liver Cirrhosis; Cholestasis; Gallbladder Diseases; Gallbladder; Male; Mice, Knockout
PubMed: 38934703
DOI: 10.1097/HC9.0000000000000473 -
Heliyon Jun 2024The impact of seawater intrusion from coast to inland terrain in the Cauvery River Basin (CRB) and Uppanar River Basin (URB) was evaluated based on major ion groundwater...
The impact of seawater intrusion from coast to inland terrain in the Cauvery River Basin (CRB) and Uppanar River Basin (URB) was evaluated based on major ion groundwater chemistry. TDS ranges from 229 to 2260 mg/l, and 408 to 3732 mg/l; Na range from 67 to 560 mg/l, and 74 to 1600 mg/l, and Cl range from 120 to 906 mg/l, and 110 to 3260 mg/l for CRB and URB respectively. Piper Diagram, Hydrochemical Facies Evolution Diagram (HFE-D), rock-water interaction (Gibbs Plots), various bivariate plots viz., TDS vs. Cl; Na vs. Cl; Ca vs. Cl; Ca vs. SO ; TH vs. TDS and Principal Component Analysis (PCA) (Cluster and Factor analysis) were used to identify the seawater intrusion from coast to inland aquifers and to understand hydrogeochemical characterization and salinization processes. Piper diagram shows that most of the samples are Na-Cl type, HFE-D diagram also shows that most of the samples were saline intrusion type and mixing behavior, while TH TDS plot shows hard fresh to hard brackish type from both the basins. PCA results clearly show the three factors, explaining 84.02 % and 76.67 % variance in URB and CRB. Factor-1 records 53.03 % alteration, with a strong confidence loading of TDS, Na, Cl, Ca, K, SO , Total Alkalinity (TA), and Total Hardness (TH) in URB indicating saline nature. A total variance of 46.23 % in CBR is more positively loaded with TH, Mg, Ca, and SO indicating rock-water interaction. Cluster analyses of these parameters illustrate the cluster distribution in CRB and URB. In URB, TDS, Na, and Cl ions make a cluster with a linkage distance of 5000 m, whereas in CRB, the TDS, Na, Cl, and TA ions make a cluster with a linkage distance of 2800 m. The factor and cluster analysis fetched out an effect of intensive use of fertilizers, aquaculture activities, and excessive groundwater exploitation. This technique gave the relationship between various chemical parameters in groundwater. Factor and cluster analysis have proven highly effective in groundwater quality studies. The study concluded that the study area has the threat of saline water intrusion in shallow aquifers with continuous influences of seawater mixing.
PubMed: 38933963
DOI: 10.1016/j.heliyon.2024.e32396 -
Heliyon Jun 2024The study assesses the mechanical efficiency, long-lasting characteristics, microstructure, and sustainability of sustainable concrete (SC) samples through several...
The study assesses the mechanical efficiency, long-lasting characteristics, microstructure, and sustainability of sustainable concrete (SC) samples through several optimization methods, emphasizing the significance of the 3Rs (recycle, reuse, reduce) approach in the construction sector. The study uses advanced techniques like the Taguchi method, grey relational analysis (GRA), analysis of variance (ANOVA), and signal-noise ratio (SNR) to optimize parameters affecting the performance of SC. In this study, the properties of SC are assessed by considering various parameters. These parameters include the use of 10 %, 20 %, and 30 % of ground granulated blast furnace slag (GGBFS) as a replacement for fly ash (FA). Additionally, six different binder contents ranging from 300 kg/m to 600 kg/m are examined. The study also investigates three different molarities of sodium hydroxide (NaOH) (8 M, 12 M, and 16 M), three different ratios of alkaline activators (AA) (1.5, 2.0, and 2.5), three different AA to-binder ratios (0.30, 0.35, and 0.40), and curing temperature (CT) of 30 °C, 60 °C, and 90 °C. The study includes fresh properties such as fresh density (FD) and slump, mechanical properties such as tensile strength (TS), flexural strength (FS), modulus of elasticity (MOE), and compressive strength (CS), and durability studies such as dry density (DD), impact strength, water absorption (WA), and sorptivity. The blended proportions were obtained using the Taguchi method. The study shows that GGBFS accelerates geopolymerization in FA-based concrete, reducing setting time and early-age CS. FA is crucial for setting time, workability, and CS enhancement. GGBFS increases the densities of fresh and hardened concrete, with a highly correlated increase, allowing accurate hardened density prediction with a coefficient of 0.9057. The CS of the cube SC surpassed 40 MPa, irrespective of variables such as the AA ratio, CT, and NaOH molarity. The trail mix with a binder concentration of 600 kg/m, 30 % GGBFS content, 12 M NaOH molarity, 1.5 AA ratio, 0.35 AA to binder ratio, and 90 °C CT exhibited the greatest strength. Mixtures containing 10 % GGBFS can attain a CS above 30 MPa after 28 days, making them suitable for structural purposes. The T mix exhibited a compact Calcium (alumino) silicate hydrate (C-A-S-H) and N-A-S-H gel, whereas the T mix displayed a varied and permeable structure. The study used GRA, ANOVA, and SNR methods to analyze properties varying by six variables, finding GGBFS content as the most influencing parameter. The study found that the SC had a lower sustainability score than the OPC mix, but had better energy efficiency.
PubMed: 38933962
DOI: 10.1016/j.heliyon.2024.e32206 -
Cureus May 2024Background Brain cancer, particularly glioblastoma (GBM), is a global health problem. Despite therapy advances, GBM patients have a poor prognosis. The progression and...
Background Brain cancer, particularly glioblastoma (GBM), is a global health problem. Despite therapy advances, GBM patients have a poor prognosis. The progression and etiology of GBM may be linked to gene polymorphisms in the , , and genes, among others. However, the genetic variations and their interaction in GBM are not fully understood. This study examines the effects of mutations in the , , and genes on GBM. Methodology Tissue and blood samples were obtained for hematological, biochemical, and genetic analysis from 18 patients diagnosed with GBM as well as 28 healthy individuals. Standard methods were adopted to perform hematological and biochemical analyses, whereas mutational landscape and expression profiles were obtained from publicly accessible databases. Tissue samples were processed for genomic DNA extraction, and genotype determination was carried out through conventional polymerase chain reaction (PCR) and Sanger sequencing. Results The study involved 18 patients with grade IV GBM before treatment and 28 healthy individuals. The patients consisted of 11 men (61%) and seven females (39%), while healthy individuals included 14 (50%) males and 14 (50%) females. Sixty-seven percent of patients were under 50, 17% between 51 and 60, and 17% over 61, compared to healthy individuals who were 61% under 50, 7% between 51 and 60, and 32% over 60. GBM patients showed higher neutrophil and monocyte counts (median 81% (63.9, 83.5) and 4.2% (3.8-7.3)), respectively, and lower lymphocyte counts (median 13.4% (8.8, 28.40)) compared to controls. The median values of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed no significant differences between the control and GBM groups. GBM patients had significantly higher median CRP levels of 2.55 (1.6, 98) than controls. Analysis of databases revealed a high prevalence of mutations in , with splice region variants, missense variants, and intron variants being the most common. and also displayed mutations, primarily missense and intron variants. Gene expression analysis showed significantly higher levels of and in GBM patients compared to controls. expression also exhibited a slight increase in GBM patients. Sanger sequencing identified three mutations in the gene, including a novel mutation (11915C>A) not previously reported in external databases. Additionally, novel mutations were found in the (841G>GA, 919T>TG) and (28398A>AC, 28399A>AT) genes. Conclusions This study highlights the immune dysregulation, inflammation, and genetic variations in GBM. The findings emphasize the potential importance of the , and genes as targets for therapies and diagnostic biomarkers of GBM. Further study is necessary to comprehend these genetic variations' functional implications and their use in personalized GBM treatment.
PubMed: 38933650
DOI: 10.7759/cureus.61165 -
Innovation (Cambridge (Mass.)) Jul 2024Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct...
Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct routes. Entomopathogenic fungi are primarily believed to infect host insects through external cuticle penetration. Here, we report a new variety, var. (Bbm), that can infect insects through the previously unrecognized foregut. Dual routes of infection significantly accelerate insect mortality. The pH-responsive transcription factor PacC in Bbm exhibits rapid upregulation and efficient proteolytic processing via PalC for alkaline adaptation in the foregut. Expression of is regulated by the adjacent downstream gene . Compared to non-enteropathogenic strains such as ARSEF252, in Bbm lacks a 249-bp fragment, resulting in its enhanced alkaline-induced expression. This induction promotes upregulation and facilitates PacC activation. Expressing the active form of BbmPacC in ARSEF252 enables intestinal infection. This study uncovers the pH-responsive Aia-PalC-PacC cascade enhancing fungal alkaline tolerance for intestinal infection, laying the foundation for developing a new generation of fungal insecticides to control destructive insect pests.
PubMed: 38933340
DOI: 10.1016/j.xinn.2024.100644 -
Acta Endocrinologica (Bucharest,... 2023Different vitamin D analogs might have advantages over calcitriol.
THE EFFECT OF PARICALCITOL AND CALCITRIOL WITH OR WITHOUT CALCIMIMETICS ON PULSE WAVE VELOCITY AND SERUM LEVELS FOR PARATHYROID HORMONE, CALCIUM AND PHOSPHORUS IN MAINTENANCE HEMODIALYSIS PATIENTS.
CONTEXT
Different vitamin D analogs might have advantages over calcitriol.
OBJECTIVE
To evaluate the effects of paricalcitol . calcitriol based vitamin D receptor activators on calcium-phosphate metabolism and pulse wave velocity in hemodialysis patients.
DESIGN
Observational, cross-sectional and 1 year follow-up study.
SUBJECTS AND METHODS
181 hemodialysis patients were enrolled in this study as divided in to 5 groups based on vitamin D therapy. Baseline and 12 month data on blood biochemistry, pulse wave velocity and cumulative dose of treatments were compared in each study group as well as in overall paricalcitol . calcitriol-based treatment groups.
RESULTS
From baseline to 12 month, significant improvement in pulse wave velocity and parathyroid hormone was shown in paricalcitol-based treatment group without a significant change in calcium, phosphate, alkaline phosphatase. A significant increase in pulse wave velocity, serum phosphate levels, calcium x phosphate product and serum alkaline phosphatase levels were noted in calcitriol-based treatment group with no significant change in serum calcium and parathyroid hormone levels.
CONCLUSION
Our findings revealed superiority of paricalcitol than calcitriol based vitamin D receptor activator therapy in terms of serum phosphate levels, CaxP product, dose requirement for vitamin D and the control of pulse wave velocity.
PubMed: 38933256
DOI: 10.4183/aeb.2023.480 -
Fundamental Research May 2024
PubMed: 38933193
DOI: 10.1016/j.fmre.2024.03.012 -
Neuropsychiatric Disease and Treatment 2024In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to...
PURPOSE
In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia.
PATIENTS AND METHODS
We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed.
RESULTS
The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3, CD3CD4 and CD3CD8 cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS).
CONCLUSION
Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.
PubMed: 38933096
DOI: 10.2147/NDT.S462496 -
Viruses Jun 2024Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked...
Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.
Topics: Enzyme-Linked Immunosorbent Assay; Humans; Respiratory Syncytial Virus Infections; Antibodies, Viral; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Infant; Child, Preschool; Adult; Child; Adolescent; Middle Aged; Young Adult; Female; Sensitivity and Specificity; Antigens, Viral; Male; Viral Fusion Proteins; Aged
PubMed: 38932244
DOI: 10.3390/v16060952 -
Pharmaceutics Jun 2024Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to... (Review)
Review
Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, , and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with supplementation with natural products may confer benefits to cancer patients, by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.
PubMed: 38931908
DOI: 10.3390/pharmaceutics16060787