Laparoscopic splenectomy (LS) being used after Transjugular intrahepatic portosystemic shunt (TIPS) has not been reported. This report aims to explore the feasibility, safety, and potential efficacy of LS after TIPS hypersplenism secondary to portal hypertension (PHT).

We retrospectively reviewed a series of six patients who underwent LS after TIPS for hypersplenism secondary to PHT between 2014 and 2020. The perioperative data and patients' clinical outcomes were recorded.

LS was successfully performed in all patients. Hypersplenism was corrected after LS in all six patients. Postoperative prothrombin time, prothrombin activity, international normalized ratio, and total bilirubin showed a trend toward improvement. The preoperative and 1-month postoperative albumin and activated partial thromboplastin levels showed no significant difference. Plasma ammonia level and thromboelastography indicators were ameliorated in two limited recorded patients. No postoperative complications such as subphrenic abscess, portal vein thrombosis, variceal bleeding, hepatic encephalopathy, and liver failure occurred during the 1-month follow-up period.

LS following TIPS is feasible, safe, and beneficial for patients with hypersplenism secondary to PHT. The following LS not only corrects the hypersplenism, but also has the potential to improve liver function.
LS following TIPS is feasible, safe, and beneficial for patients with hypersplenism secondary to PHT. The following LS not only corrects the hypersplenism, but also has the potential to improve liver function.
Understanding intervention delivery as intended, particularly in complex interventions, should be underpinned by good quality fidelity assessment. We present the findings from a fidelity assessment embedded as part of a trial of a complex community-based psychosocial intervention, Journeying through Dementia (JtD). The intervention was designed to equip individuals with the knowledge and skills to successfully self-manage, maintain independence, and live well with dementia and involves both group and individual sessions. The methodological challenges of developing a conceptual framework for fidelity assessment and creating and applying purposely designed measures derived from this framework are discussed to inform future studies.

A conceptual fidelity framework was created out of core components of the intervention (including the intervention manual and training for delivery), associated trial protocols and pre-defined fidelity standards and criteria against which intervention delivery and receipt could bterventionists concurred with researcher assessments.

There was good fidelity to training and delivery of the group aspect of the intervention at four sites. However, the methodological challenges of assessing all aspects of this complex intervention could not be overcome due to practicalities, assessment methods and ethical considerations. Questions remain regarding how we can assess fidelity in community-based complex interventions without impacting upon intervention or trial delivery.

ISRCTN17993825 .
ISRCTN17993825 .
Neurodegenerative diseases have become the rising cause of various disabilities worldwide, followed by aging, including Parkinson's disease (PD). Parkinson's disease is a degenerative brain disorder distinguished by growing motor & non-motor failure due to the degeneration of medium-sized spiked neurons in the striatum region. Rotenone is often employed to originate the animal model of PD. It is a powerful blocker of mitochondrial complex-I, mitochondrial electron transport chain that reliably produces Parkinsonism-like symptoms in rats. Rice bran (RB) is very rich in polyunsaturated fatty acids (PUFA) and nutritionally beneficial compounds such as γ-oryzanol, tocopherols, and tocotrienols and sterols are believed to have favorable outcomes on oxidative stress & mitochondrial function.

The present study has been designed to explore RB extract's effect against rotenone-induced neurotoxicity in rats.

In the present study, Rotenone (2 mg/kg, s.c) was administered systemically for 28 days. The hexan may underlie the adjuvant susceptibility towards rotenone-induced PD in experimental rats.
The findings support that PD is associated with impairments in motor activity. The results also suggest that the nutraceutical rice bran that contains γ-oryzanol, Vitamin-E, ferulic acid etc., may underlie the adjuvant susceptibility towards rotenone-induced PD in experimental rats.Hormonal coordination is tightly regulated within the human body and thus regulates human physiology. The parathyroid hormone (PTH), a member of the endocrine system, regulates the calcium and phosphate level within the human body. Under non-physiological conditions, PTH levels get upregulated (hyperparathyroidism) or downregulated (hypoparathyroidism) due to external or internal factors. https://www.selleckchem.com/products/xl413-bms-863233.html In the case of hyperparathyroidism, elevated PTH stimulates cellular receptors present in the bones, kidneys, and intestines to increase the blood calcium level, leading to calcium deposition. This eventually causes various symptoms including kidney stones. Currently, there is no known medication that directly targets PTH in order to suppress its function. Therefore, it is of great interest to find novel small molecules or any other means that can modulate PTH function. The molecular signaling of PTH starts by binding of its N-terminus to the G-protein coupled PTH1/2 receptor. Therefore, any intervention that affects the N-terminus of PTH could be a lead candidate for treating hyperparathyroidism. As a proof-of-concept, there are various possibilities to inhibit molecular PTH function by (i) a small molecule, (ii) N-terminal PTH phosphorylation, (iii) fibril formation and (iv) residue-specific mutations. These modifications put PTH into an inactive state, which will be discussed in detail in this review article. We anticipate that exploring small molecules or other means that affect the N-terminus of PTH could be lead candidates in combating hyperparathyroidism.
Medicinal plants and herbal preparations in the form of traditional medicines have been used in healthcare worldwide. The extracts of Ginkgo biloba L. seeds and leaves contain a complex mixture of numerous components, such as flavonol glycosides, terpene lactones, and a group of alkylphenols (anacardic or ginkgolic acids, cardanols and cardols) that have been a part of traditional Chinese medicine. These extracts are also sold as dietary supplements worldwide. G. biloba extract (EGb 761 and LI 1370) represent the standard form of G. biloba extract. Six different 6-alkylsalicylic acids (syn. ginkgolic acids) with alkyl substituents (C130, C150, C151, C171, and C172) have been identified.

To aim of this review is to unravel scientific evidences on anti-inflammatory and anticancer activities of ginkgolic acids to understand its therapeutic potential against inflammatory and oncologic diseases.

A structured literature search was independently performed by the authors on PubMed, ScienceDirect, Scopus, and Weof these natural agents are warranted before clinical transition.
In this review, we present updated information on the anti-inflammatory and anticancer properties of ginkgolic acids both in vitro and in vivo. Although ginkgolic acids show significant therapeutic potential in inflammatory and oncologic diseases, more investigations regarding the safety and efficacy of these natural agents are warranted before clinical transition.
Hepatocellular carcinoma (HCC) is the 6th prevalent cancer and the 4th leading cause of cancer related deaths all over the world. A major challenge for sorafenib, the standard chemotherapeutic agent in HCC treatment, is the chemo-resistance.

This study was conducted to evaluate the role of dantrolene as a possible antineoplastic agent in HCC, and in chemo-sensitization of sorafenib via targeting Ca+2/PI3K pathway.

HCC was induced in rats using a single dose of diethyl nitrosamine (DENA) (200 mg/kg, ip), followed by phenobarbital sodium (0.05%) in drinking water for 18 weeks. link2 At the end of 18th week, rats were allocated into 4 groups (10 rats/each), one group was left without treatment (DENA group) and the other three groups were treated with either sorafenib, dantrolene, or their combination for further 4 weeks. One day after last injection, serum and liver tissues were collected. Liver tissue p53, VEGF, MMP-9, Cyclin D1, PI3K, and, serum AFP were assessed using immunoassay. link3 Hepatic and serum Ca+2 were also computed. Furthermore, Ki67 was assessed immunohistochemically.

Dantrolene exhibited synergistic effect when used in combination with sorafenib compared to either drug alone (p <0.05) through decreasing p53, VEGF, MMP-9, Cyclin D1, and Ki-67. In addition, dantrolene was evidenced to have an inhibitory effect on Ca+2/PI3K pathway that mediates its antineoplastic action when used alone or in combination with sorafenib.

Dantrolene exerted antineoplastic effect as well as augmented sorafenib antineoplastic activity via intervention of Ca+2/PI3K pathway, manifested by ameliorating angiogenesis, apoptosis, proliferation and metastasis.
Dantrolene exerted antineoplastic effect as well as augmented sorafenib antineoplastic activity via intervention of Ca+2/PI3K pathway, manifested by ameliorating angiogenesis, apoptosis, proliferation and metastasis.The recent developments in epigenetics have shown a very important role of epigenetic changes in cancer initiation, development, and progression. Some of the important histone modifications shown to occur are methylation, acetylation, phosphorylation, citrullination, sumoylation, ADP ribosylation, deamination, ubiquitination, formylation, O-GlcNAcylation, propionylation, butyrylation, proline isomerization, and crotonylation but most of the studies in past had limited their studies mainly on histone methylation, acetylation, and phosphorylation. Modification of DNA strand by hypermethylation and hypomethylation regulates genomic instability and promotes cancer. Colorectal cancer involves multiple changes in epigenetic marks present on histone residues and DNA, which in collaboration with genetic changes, drives cancer progression. In this review paper, basic concepts of epigenetics relevant to cancer development are discussed followed by its significance in understanding the mechanism of colon carcinogenesis. Some of the epigenetic target based drugs are also discussed in the relevant sections to give an idea of the potential promises of epigenetics for colorectal cancer treatment.
In human tauopathies, pathological aggregation of misfolded/unfolded proteins particularly microtubule-associated protein tau (MAPT, tau) is considered to be essential mechanisms that trigger the induction of endoplasmic reticulum (ER) stress.

Here we assessed the molecular effects of natural antioxidant alpha-lipoic acid (ALA) in human tauR406W (htau)-induced ER unfolded protein response (ERUPR) in fruit flies.

In order to reduce htau neurotoxicity during brain development, we used a transgenic model of tauopathy where the maximum toxicity was observed in adult flies. Then, the effects of ALA (0.001, 0.005, and 0.025% w/w of diet) in htau-induced ERUPR and behavioral dysfunctions in the ages 20 and 30 days were evaluated in Drosophila melanogaster.

Data from expression (mRNA and protein) patterns of htau, analysis of eyes external morphology as well as larvae olfactory memory were confirmed our tauopathy model. Moreover, expression of ERUPR-related proteins involving activating transcription factor 6 (ATF6), inositol regulating enzyme 1 (IRE1), and protein kinase RNA-like ER kinase (PERK) were upregulated and locomotor function decreased in both ages of the model flies.