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| 1 | Macrophages in metabolic associated fatty liver disease显示文摘Metabolic associated fatty liver disease(MAFLD),formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries.The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis,hepatocellular carcinoma,liver transplantation,and death,but also to extrahepatic complications including cardiovascular disease,diabetes and chronic kidney disease.The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development.This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis,inflammation,fibrosis,and hepatocellular carcinoma,as well as for the extra-hepatic manifestations of MAFLD.We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes,hepatic stellate cells,and adipose tissue.We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD. | Jawaher Alharthi Olivier Latchoumanin Jacob George Mohammed Eslam | 2020 | World Journal of Gastroenterology2020，26，16： | 5 |
| 2 | Residual feed intake divergence during the preweaning period is associated with unique hindgut microbiome and metabolome profiles in neonatal Holstein heifer calves显示文摘Background:Recent studies underscored that divergence in residual feed intake(RFI)in mature beef and dairy cattle is associated with changes in ruminal microbiome and metabolome profiles which may contribute,at least in part,to better feed efficiency.Because the rumen in neonatal calves during the preweaning period is underdeveloped until close to weaning,they rely on hindgut microbial fermentation to breakdown undigested diet components.This leads to production of key metabolites such as volatile fatty acids(VFA),amino acids,and vitamins that could potentially be absorbed in the hind-gut and help drive growth and development.Whether RFI divergence in neonatal calves is associated with changes in hindgut microbial communities and metabolites is largely unknown.Therefore,the objective of the current study was to determine differences in hindgut microbiome and metabolome in neonatal Holstein heifer calves retrospectively-grouped based on feed efficiency as mostefficient(M-eff)or least-efficient(L-eff)calves using RFI divergence during the preweaning period.Methods:Twenty-six Holstein heifer calves received 3.8 L of first-milking colostrum from their respective dams within 6 h after birth.Calves were housed in individual outdoor hutches bedded with straw,fed twice daily with a milk replacer,and had ad libitum access to a starter grain mix from birth to weaning at 42 d of age.Calves were classified into M-eff[n=13;RFI coefficient=−5.72±0.94 kg DMI(milk replacer+starter grain)/d]and L-eff[n=13;RFI coefficient=5.61±0.94 kg DMI(milk replacer+starter grain)/d]based on a linear regression model including the combined starter grain mix and milk replacer DMI,average daily gain(ADG),and metabolic body weight(MBW).A deep sterile rectal swab exposed only to the rectum was collected immediately at birth before colostrum feeding(i.e.,d 0),and fecal samples at d 14,28,and 42(prior to weaning)for microbiome and untargeted metabolome analyses using 16S rRNA gene sequencing and LC-MS.Microbiome data were analyzed with the QIIME 2 platform and metabolome data with the MetaboAnalyst 4.0 pipeline.Results:No differences(P>0.05)in body measurements including body weight(BW),body length(BL),hip height(HH),hip width(HW),and wither height(WH)were detected between M-eff and L-eff calves at birth and during preweaning.Although milk replacer intake did not differ between groups,compared with L-eff,M-eff heifers had lower starter intake(P<0.01)between d 18 to 42 of age,whereas no differences(P>0.05)for ADG,cumulative BWG,or body measurements were observed between RFI groups during the preweaning period.Microbiome and metabolome profiles through the first 42 d of age indicated greater hindgut capacity for the production of energy-generating substrates(butyrate and propionate)and essential nutrients(vitamins and amino acids)in heifers with greater estimated feed efficiency.Conclusion:Despite consuming approximately 54.6%less solid feed(cumulative intake,10.90 vs.19.98±1.66 kg)from birth to weaning,the microbiome-metabolome changes in the hindgut of most-efficient heifers might have helped them maintain the same level of growth as the least-efficient heifers. | Ahmed Elolimy Abdulrahman Alharthi Mohamed Zeineldin Claudia Parys Juan J.Loor | 2020 | Journal of Animal Science and Biotechnology2020，11，2： | 4 |
| 3 | Biomarkers of Metabolic(Dysfunction)-associated Fatty Liver Disease:An Update显示文摘The prevalence of metabolic(dysfunction)-associated fatty liver disease(MAFLD)is rapidly increasing and affects up to two billion individuals globally,and this has also resulted in increased risks for cirrhosis,hepatocellular carcinoma,and liver transplants.In addition,it has also been linked to extrahepatic consequences,such as cardiovascular disease,diabetes,and various types of cancers.However,only a small proportion of patients with MAFLD develop these complications.Therefore,the identification of high-risk patients is paramount.Liver fibrosis is the major determinant in developing these complications.Although,liver biopsy is still considered the gold standard for the assessment of patients with MAFLD.Because of its invasive nature,among many other limitations,the search for noninvasive biomarkers for MAFLD remains an area of intensive research.In this review,we provide an update on the current and future biomarkers of MAFLD,including a discussion of the associated genetics,epigenetics,microbiota,and metabolomics.We also touch on the next wave of multiomic-based biomarkers. | Jawaher Alharthi Mohammed Eslam | 2022 | Journal of Clinical and Translational Hepatology2022，10，1： | 3 |
| 4 | Body condition score prior to parturition is associated with plasma and adipose tissue biomarkers of lipid metabolism and inflammation in Holstein cows显示文摘Background: Previous research has revealed a strong inflammatory response within adipose(AT) tissue during the transition into lactation. Whether this effect is a result of oxidative stress induced by lipolysis and fatty acid oxidation associated with differences in prepartum body condition score remains to be determined. The objectives of this study were to investigate systemic biomarkers of energy balance and inflammation and the expression of lipid metabolismand inflammation-related genes in AT during the transition period in dairy cows.Results: Twenty multiparous Holstein cows were retrospectively divided by body condition score(BCS) prior to parturition into two groups(10 cows/group): BCS ≤ 3.25(Lo BCS) and BCS ≥ 3.75(Hi BCS). Subcutaneous adipose tissue was biopsied from the tail-head region at d-10, 7 and 20 relative to parturition. Plasma was used to evaluate biomarkers of energy balance(EBAL) [free fatty acids(NEFA), glycerol, insulin] and inflammation [IL-1β, haptoglobin, myeloperoxidase, and reactive oxygen metabolites(ROM)]. Although insulin concentration was not affected by BCS, NEFA was overal greater and glycerol lower in HiB CS cows. Greater activity of myeloperoxidase in plasma coincided with increased haptoglobin and IL-1β postpartum in LoB CS cows.Among genes related with oxidative stress, the expression of the cytosolic antioxidant enzyme SOD1 was greater in LoB CS compared to HiB CS. Cows in LoB CS compared with HiB CS had greater overal expression of ABDH5 and ATGL along with ADIPOQ, indicating enhanced basal lipolysis and secretion of adiponectin. Expression of CPT1 A, ACADVL, and ACOX1 was greater overal in HiB CS than LoB CS indicating enhanced NEFA oxidation. Although the temporal increase in plasma NEFA regardless of BCS coincided with the profile of CPT1 A, the gradual decrease in genes related with reesterification of NEFA(PCK1) and glycerol efflux(AQP7) coupled with an increase in glycerol kinase(GK) suggested some stimulation of NEFA utilization within adipose tissue. This idea is supported in part by the gradual decrease in insulin regardless of BCS. Although expression of the inflammation-related gene toll-like receptor 4( TLR4) was greater in Hi BCS versus Lo BCS cows at-10 d, expression of TLR9 was greater in Hi BCS versus Lo BCS at 20 d.These profiles did not seem to be associated with concentrations of pro-inflammatory biomarkers or ROM.Conclusions: Overall, data indicated that cows with BCS 3.25 or lower before calving experienced greater alterations in systemic inflammation and basal lipolysis without excessive increases in NEFA plasma concentrations.Despite the greater plasma NEFA around parturition, cows with BCS 3.75 or higher seemed to have a more active system for catabolism of NEFA and utilization of glycerol within adipose tissue. A linkage between those pathways and risk of disorders postpartum remains to be determined. | Abdulrahman Alharthi Zheng Zhou Vincenzo Lopreiato Erminio Trevisi Juan J.Loor | 2018 | Journal of Animal Science and Biotechnology2018，9，2： | 3 |
| 5 | Association of HLA loci alleles and antigens in Saudi patients with vitiligo 显示文摘 | Abanmi A AlHarthi F AlBaqami R | 2006 | Arch Dermatol Res2006，298，7： | 1 |
| 6 | Cinacalcet in pediatric and adolescent chronic kidney disease显示文摘 | Alharthi AA Kamal NM Sherief LM | 2013 | Medicine(Baltimore)2013，94，2： | 1 |
| 7 | Selective echocardiographic analysis of epicardial and endocardial left ventricular rotational mechanics in an animal model of pericardial adhesions显示文摘 | Alharthi MS Jiamsripong P Calleja A | | 0，，03： | 1 |
| 8 | The impact of attrition on vocabulary knowledge among Saudi teachers 显示文摘 | Alharthi T | 2014 | English Language Teaching2014，7，4： | 1 |
| 9 | Metabolic associated fatty liver disease(MAFLD):a milestone in the history of fatty liver disease显示文摘With the widespread increase in energy intake and physical inactivity,the prevalence of metabolic health is declining.Consequently,metabolic associated fatty liver disease(MAFLD)[formerly known as non-alcoholic fatty liver disease(NAFLD)]has risen in prevalence and present a significant challenge to global health causing considerable morbidity and mortality,particularly when fibrosis is present(1). | Jawaher Alharthi Mohammed Eslam | 2021 | Hepatobiliary Surgery and Nutrition2021，10，5： | 1 |
| 10 | Evaluation of left ventricular rotation in obese subjects by velocity vector imaging显示文摘 | Deng Y Alharthi MS Thota VR | 2010 | Eur J Echocardiogr2010，，： | 1 |
| 11 | Quantification of left ventricular twisting mechanics by velocity vector imaging in an animal model of pericardial adhesions显示文摘 | Jiamsripong P Alharthi MS Calleja AM | 2009 | Ultrasound Med Biol2009，35，12： | 1 |
| 12 | Correlation of automatedfunction imaging( AFI) to conventional strain analyses of regional andglobal right ventricular function 显示文摘 | Calleja AM Jiamsripong P Alharthi MS | 2009 | J Am Soc Echocardiogr2009，22，9： | 1 |
| 13 | Spontaneous gastric ulcer perforation and acute spleen infarction caused by invasive gastric and splenic mucormycosis显示文摘 | Enani M A Alharthi B N Dewanjee N | 2014 | J Glob Infect Dis2014，6，3： | 1 |
| 14 | Soil water saturation:dielectric determination显示文摘 | Alharthi A Lange J | 1987 | Water Resources Research1987，23，4： | 1 |
| 15 | Neoadjuvant chemotherapy in locally advanced breast cancer显示文摘 | Iqbal J Shafi AA Alharthi BN | 2014 | J Coll Physicians Surg Pak2014，24，11： | 1 |
| 16 | Expression of fatty acid sensing G-protein coupled receptors in peripartal Holstein cows显示文摘Background: G-protein coupled receptors(GPCR), also referred as Free Fatty Acid Receptors(FFAR), are widely studied within human medicine as drug targets for metabolic disorders. To combat metabolic disorders prevalent in dairy cows during the transition period, which co-occur with negative energy balance and changes to lipid and glucose metabolism, it may be helpful to identify locations and roles of FFAR and other members of the GPCR family in bovine tissues.Results: Quantitative RT-PCR(qPCR) of subcutaneous adipose, liver, and PMNL samples during the transition period(-10, +7, and +20 or +30 d) were used for expression profiling of medium-(MCFA) and long-chain fatty acid(LCFA)receptors GPR120 and GPR40, MCFA receptor GPR84, and niacin receptor HCAR2/3. Adipose samples were obtained from cows with either high(HI; BCS ≥ 3.75) or low(LO; BCS ≤ 3.25) body condition score(BCS) to examine whether FFAR expression is correlated with this indicator of health and body reserves. Supplementation of rumen-protected methionine(MET), which may improve immune function and production postpartum, was also compared with unsupplemented control(CON) cows for liver and blood polymorphonuclear leukocytes(PMNL) samples. In adipose tissue, GPR84 and GPR120 were differentially expressed over time, while GPR40 was not expressed; in PMNL, GPR40 was differentially expressed over time and between MET vs. CON, GPR84 expression differed only between dietary groups, and GPR120 was not expressed; in liver, GPCR were either not expressed or barely detectable.Conclusions: The data indicate that there is likely not a direct role in liver for the selected GPCR during the transition period, but they do play variable roles in adipose and PMN. In future, these receptors may prove useful targets and/or markers for peripartal metabolism and immunity. | Alea Agrawal Abdulrahman Alharthi Mario Vailati-Riboni Zheng Zhou Juan J.Loor | 2017 | Journal of Animal Science and Biotechnology2017，8，3： | 1 |
| 17 | Illicit drug abuse affects periodontal health status显示文摘 | Kayal RA Elias WY Alharthi K J | 2014 | Saudi Med J2014，35，7： | 1 |
| 18 | Prediction of incipi- ent left ventricular dysfunction in patients with chronic primary mitral regurgitation: a velocity vector imaging study 显示文摘 | Moustafa SE Kansal M Alharthi M | 2011 | Eur J Echocardiogr2011，12，4： | 1 |
| 19 | Prediction of incipient left ventricular dysfunction in patients with chronic primary mitral regurgitation: a velocity vector imaging study显示文摘 | Moustafa SE Kansal M Alharthi M | 2011 | Eur J Echocardiogr2011，12，4： | 1 |
| 20 | Manifestations of type 2 diabetes in corneal endothelial cell density,corneal thickness and intraocular pressure显示文摘We sought to evaluate central corneal thickness(CCT),corneal endothelial cell density(ECD)and intraocular pressure(IOP)in patients with type 2 diabetes mellitus(DM)and to associate potential differences with diabetes duration and treatment modality in a prospective,randomized study.We measured ECD,CCT and IOP of125 patients with type 2 DM(mean age 57.1±11.5 years)and compared them with 90 age-matched controls.Measured parameters were analyzed for association with diabetes duration and glucose control modalities(insulin injection or oral medication)while controlling for age.In the diabetic group,the mean ECD(2511±252 cells/mm^2),mean CCT(539.7±33.6μm)and mean IOP(18.3±2.5 mmHg)varied significantly from those the control group[ECD:2713±132 cells/mm^2(P<0.0001),CCT:525.0±45.3μm(P=0.003)and IOP:16.7±1.8 mmHg(P<0.0001)].ECD was significantly reduced by about 32 cell/mm^2 for diabetics with duration of>10 years when compared with those with duration of<10 years(P<0.05).CCT was thicker and IOP was higher for diabetics with duration of>10 years than those with duration of<10 years(P>0.05).None of the measured parameters was significantly associated with diabetes duration and treatment modality(P>0.05).In conclusion,subjects with type 2DM exhibit significant changes in ECD,IOP and CCT,which,however,are not correlated with disease duration or if the patients receive on insulin injection or oral medications. | Stella Briggs Uchechukwu L Osuagwu Essam M AlHarthi | 2016 | The Journal of Biomedical Research2016，30，1： | 1 |
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