Genta Kakiyama
Dec 1, 2020; 61:1629-1644
Research Articles

Abudukadier Abulizi
Dec 1, 2020; 61:1565-1576
Research Articles

NAFLD is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to NASH remain unclear. This lack of knowledge leads to a decreased ability to find relevant animal models, predict disease progression, or develop clinical treatments. In the current study, we used multiple mouse models of NAFLD, human correlation data, and selective gene overexpression of steroidogenic acute regulatory protein (StarD1) in mice to elucidate a plausible mechanistic pathway for promoting the transition from NAFL to NASH. We show that oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the "acidic/alternative" pathway of cholesterol metabolism. Specifically, we report data showing that an inability to upregulate CYP7B1, in the setting of insulin resistance, results in the accumulation of toxic intracellular cholesterol metabolites that promote inflammation and hepatocyte injury. This metabolic pathway, initiated and exacerbated by insulin resistance, offers insight into approaches for the treatment of NAFLD.

Microsomal triglyceride transfer protein (MTTP) deficiency results in a syndrome of hypolipidemia and accelerated NAFLD. Animal models of decreased hepatic MTTP activity have revealed an unexplained dissociation between hepatic steatosis and hepatic insulin resistance. Here, we performed comprehensive metabolic phenotyping of liver-specific MTTP knockout (L-Mttp^–/–) mice and age-weight matched wild-type control mice. Young (10–12-week-old) L-Mttp^–/– mice exhibited hepatic steatosis and increased DAG content; however, the increase in hepatic DAG content was partitioned to the lipid droplet and was not increased in the plasma membrane. Young L-Mttp^–/– mice also manifested normal hepatic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamps, no PKC activation, and normal hepatic insulin signaling from the insulin receptor through AKT Ser/Thr kinase. In contrast, aged (10-month-old) L-Mttp^–/– mice exhibited glucose intolerance and hepatic insulin resistance along with an increase in hepatic plasma membrane sn-1,2-DAG content and PKC activation. Treatment with a functionally liver-targeted mitochondrial uncoupler protected the aged L-Mttp^–/– mice against the development of hepatic steatosis, increased plasma membrane sn-1,2-DAG content, PKC activation, and hepatic insulin resistance. Furthermore, increased hepatic insulin sensitivity in the aged controlled-release mitochondrial protonophore-treated L-Mttp^–/– mice was not associated with any reductions in hepatic ceramide content. Taken together, these data demonstrate that differences in the intracellular compartmentation of sn-1,2-DAGs in the lipid droplet versus plasma membrane explains the dissociation of NAFLD/lipid-induced hepatic insulin resistance in young L-Mttp^–/– mice as well as the development of lipid-induced hepatic insulin resistance in aged L-Mttp^–/– mice.

Controversy over an intiative aimed a reducing inequities in Lee's Summit, Mo., schools led the police department to provide security protection for the district's first African-American superintendent. Now the school board has reversed course.

Sewage surveillance is emerging as a crucial method in combating antimicrobial resistance (AMR), according to new research from Virginia Tech. Published in Nature Water, the study demonstrates that monitoring wastewater provides a more efficient and comprehensive approach to tracking antibiotic-resistant bacteria than testing individuals. This method holds particular promise for underserved communities, where access to healthcare is limited, and AMR-related diseases are most prevalent. The research team, led by experts such as Dr. Leigh-Anne Krometis and Dr. Marc Edwards, explored sewage samples from 62 countries and found significant correlations between AMR levels and socioeconomic factors, such as healthcare accessibility. By examining wastewater, public health officials could gain early insights into AMR spread, allowing them to take targeted actions to protect vulnerable populations. This approach could revolutionise AMR monitoring, particularly in rural and low-income areas, where AMR poses a growing threat.

The people meeting in Istanbul's parks are wildly different from each other, but they are now engaging each other in ways they weren't before.

People don't realise just how bad our antibiotic resistance problem is, says Jeanne Marrazzo, the top infectious disease specialist in the US

Title: Despite Pockets of Resistance, Most U.S. Kids Getting Vaccinated
Category: Health News
Created: 8/27/2015 12:00:00 AM
Last Editorial Review: 8/28/2015 12:00:00 AM

Title: Insulin and Insulin Resistance: The Ultimate Guide
Category: Health and Living
Created: 7/19/2022 12:00:00 AM
Last Editorial Review: 7/19/2022 12:00:00 AM

Title: Insulin Resistance
Category: Diseases and Conditions
Created: 2/10/2004 12:00:00 AM
Last Editorial Review: 7/28/2022 12:00:00 AM

Solute carrier family 6 member 19 (SLC6A19) inhibitors are being studied as therapeutic agents for phenylketonuria. In this work, a potent SLC6A19 inhibitor (RA836) elevated rat kidney uremic toxin indoxyl sulfate (IDS) levels by intensity (arbitrary unit) of 13.7 ± 7.7 compared with vehicle 0.3 ± 0.1 (P = 0.01) as determined by tissue mass spectrometry imaging analysis. We hypothesized that increased plasma and kidney levels of IDS could be caused by the simultaneous inhibition of both Slc6a19 and a kidney IDS transporter responsible for excretion of IDS into urine. To test this, we first confirmed the formation of IDS through tryptophan metabolism by feeding rats a Trp-free diet. Inhibiting Slc6a19 with RA836 led to increased IDS in these rats. Next, RA836 and its key metabolites were evaluated in vitro for inhibiting kidney transporters such as organic anion transporter (OAT)1, OAT3, and breast cancer resistance protein (BCRP). RA836 inhibits BCRP with an IC₅₀ of 0.045 μM but shows no significant inhibition of OAT1 or OAT3. Finally, RA836 analogs with either potent or no inhibition of SLC6A19 and/or BCRP were synthesized and administered to rats fed a normal diet. Plasma and kidney samples were collected to quantify IDS using liquid chromatography–mass spectrometry. Neither a SLC6A19 inactive but potent BCRP inhibitor nor a SLC6A19 active but weak BCRP inhibitor raised IDS levels, whereas compounds inhibiting both transporters caused IDS accumulation in rat plasma and kidney, supporting the hypothesis that rat Bcrp contributes to the excretion of IDS. In summary, we identified that inhibiting Slc6a19 increases IDS formation, while simultaneously inhibiting Bcrp results in IDS accumulation in the kidney and plasma.

Wastewater is a major reservoir for antibiotic resistance genes, but modified bacteria can chop up this DNA before the dangerous microbes reach people

The number of people worldwide directly killed by antibiotic resistance will rise to 1.9 million a year by 2050, according to the most comprehensive study so far

Australian research has found that the widespread use of the antibiotic rifaximin is fueling the rise of a nearly untreatable superbug. (!--ref1--)

Kerala government has initiated a statewide campaign across all 14 districts to address the issue of antibiotic overuse (!--ref1--). This

medlinkHormone therapy/medlink was found to be beneficial in reducing insulin resistance in postmenopausal women, revealed study (!--ref1--). h2What

Being highly predisposed to insulin resistance puts Indians at a higher risk of developing non-alcoholic fatty liver disease (NAFLD), suggest health experts.

The Indian Medical Association (IMA) announced the formation of a powerful new alliance to tackle the escalating crisis of medlinkAntimicrobial Resistance/medlink (AMR) in India.

Infections that were once easily treatable are now becoming life-threatening due to the growing threat of Antimicrobial Resistance (AMR). This alarming trend, highlighted by Dr.

Assistant Prof. Ibrahim, Bitar, Department of Microbiology, Faculty of Medicine and University Hospital in Plzen, Charles University in Prague, Plzen,

Recent research indicates that the progressive loss of Y chromosomes in aging men significantly impairs the body's capacity to combat bladder cancer.

A breakthrough in antibiotic resistance detection has been achieved by researchers at the University of Zurich. Using cutting-edge artificial intelligence,

A new mathematical model of antibiotic resistance developed helps predict how good or poor hygiene might affect how rapidly resistant bacteria increase in abundance due to antibiotic treatment.

Chlorine disinfectant used in hospitals proves ineffective against the leading cause of medlinkantibiotic/medlink-associated sickness globally as

According to the news reported on 27 April by Kyodo News that Hirosaki University in Japan has developed electromobile with cold resistance recently, and the test drive of this electromobile has been held in Sendai on 27 of April. This...

Boulder, Colorado; London : Lynne Rienner Publishers, 2013.

Manchester : Manchester University Press, [2020]

Manchester : Manchester University Press, [2017]

Durham : Duke University Press, [2023]

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Nifty 50 November Futures contract can fall to 23,900

Here are the intraday supports and resistances for widely traded stocks such as Reliance Industries, ITC, ONGC, Infosys, HDFC Bank, TCS, and SBI

Justice Anita Sumanth refuses to issue a writ of quo warranto against seven individuals representing the Working Committee of the Residents’ Assembly

India awoke late to risks of antibiotic overuse and is scrambling to contain the surge in drug resistance.

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