Biomedical subjects

F Zhou

Publications and source records attributed to F Zhou.

At least 37 records · Page 2Linked to original sources

PubMed2001

Spin correlation and discrete symmetry in spinor Bose-Einstein condensates.

We study spin correlations in Bose-Einstein condensates of spin 1 bosons with scatterings dominated by a total spin equal 2 channel. We show that the low energy spin dynamics in the system can be mapped into an o(n) nonlinear sigma model. n = 3 at the zero magnetic field limit and n = 2 in the presence of weak magnetic fields. In an ordered phase, the ground state has a discrete Z2 symmetry and is degenerate under the group [U(1)xS(n-1)]/Z(2). We explore consequences of the discrete symmetry and propose some measurements to probe it.

Journal Article↗

PubMed2001

Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells.

4-Hydroxynonenal (HNE), a reactive and cytotoxic end-product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death and in various cell types has been shown to induce apoptosis. We have demonstrated that HNE, at micromolar concentrations, induces dose- and time-dependent apoptosis in a leukemic cell line (CEM-C7). Interestingly, much higher concentrations of HNE (> 15-fold) were required to induce apoptosis in leukocytes obtained from normal individuals. We also demonstrate that HNE causes a decrease in clonogenicity of CEM-C7 cells. Furthermore, our data characterize the caspase cascade involved in HNE-induced apoptosis in CEM-C7 cells. Using specific fluorogenic substrates and irreversible peptide inhibitors, we demonstrate that caspase 2, caspase 3, and caspase 8 are involved in HNE-induced apoptosis, and that caspase 2 is the first initiator caspase that activates the executioner caspase 3, either directly or via activation of caspase 8. Our studies also suggest the involvement of another executioner caspase, which appears to be similar to caspase 8 but not caspases 2 and 3, in its specificity. The demonstration of decreased clonogenicity by HNE in the leukemic cells, and their higher susceptibility to HNE-induced apoptosis as compared to the normal cells, suggests that such compounds may have potential for leukemia chemotherapy.

Aldehydes↗

PubMed2001

Economic analysis of a child vaccination project among Asian Americans in Philadelphia, Pa.

OBJECTIVE: To ascertain the cost-effectiveness and the benefit-cost ratios of a community-based hepatitis B vaccination catch-up project for Asian American children conducted in Philadelphia, Pa, from October 1, 1994, to February 11, 1996. DESIGN: Program evaluation. SETTING: South and southwest districts of Philadelphia. PARTICIPANTS: A total of 4384 Asian American children. INTERVENTIONS: Staff in the community-based organizations (1) educated parents about the hepatitis B vaccination, (2) enrolled physicians in the Vaccines for Children program, and (3) visited homes of children due for a vaccine dose. Staff in the Philadelphia Department of Public Health developed a computerized database; sent reminder letters for children due for a vaccine dose; and offered vaccinations in public clinics, health fairs, and homes. MAIN OUTCOME MEASURES: The numbers of children having received 1, 2, or 3 doses of vaccine before and after the interventions; costs incurred by the Philadelphia Department of Public Health and the community-based organizations for design, education, and outreach activities; the cost of the vaccination; cost-effectiveness ratios for intermediate outcomes (ie, per child, per dose, per immunoequivalent patient, and per completed series); discounted cost per discounted year of life saved; and the benefit-cost ratio of the project. RESULTS: For the completed series of 3 doses, coverage increased by 12 percentage points at a total cost of $268 660 for design, education, outreach, and vaccination. Costs per child, per dose, and per completed series were $64, $119, and $537, respectively. The discounted cost per discounted year of life saved was $11 525, and 106 years of life were saved through this intervention. The benefit-cost ratio was 4.44:1. CONCLUSION: Although the increase in coverage was modest, the intervention proved cost-effective and cost-beneficial.

Adolescent↗

PubMed2001

Increased sensitivity of mitochondrial respiration to inhibition by nitric oxide in cardiac hypertrophy.

Cardiac hypertrophy is a significant risk factor for the development of congestive heart failure (CHF). Mitochondrial defects are reported in CHF, but no consistent mitochondrial alterations have yet been identified in hypertrophy. In this study selective metabolic inhibitors were used to determine thresholds for respiratory inhibition and to reveal novel mitochondrial defects in hypertrophy. Cardiac hypertrophy was produced in rats by aortic banding. Mitochondria were isolated from left ventricular tissue and the effects of inhibiting respiratory complexes I and IV on mitochondrial oxygen consumption were measured. At 8 weeks post-surgery, 65+/-2% complex IV inhibition was required to inhibit respiration half maximally in control mitochondria. In contrast, only 52+/-6% complex IV inhibition was required to inhibit respiration half maximally in mitochondria from hypertrophied hearts (P=0.046). This effect persisted at 22 weeks post-surgery and was accompanied by a significant upregulation of inducible nitric oxide synthase (iNOS, 3.0+/-0.7-fold, P=0.006). We conclude that respiration is more sensitive to complex IV inhibition in hypertrophy. Nitric oxide is a well documented inhibitor of complex IV, and thus the combination of increased NO(.)from iNOS and an increased sensitivity to inhibition of one of its targets could result in a bioenergetic defect in hypertrophy that may be a harbinger of CHF.

Animals↗

PubMed2001

Hibernation, a model of neuroprotection.

Hibernation, a natural model of tolerance to cerebral ischemia, represents a state of pronounced fluctuation in cerebral blood flow where no brain damage occurs. Numerous neuroprotective aspects may contribute in concert to such tolerance. The purpose of this study was to determine whether hibernating brain tissue is tolerant to penetrating brain injury modeled by insertion of microdialysis probes. Guide cannulae were surgically implanted in striatum of Arctic ground squirrels before any of the animals began to hibernate. Microdialysis probes were then inserted in some animals after they entered hibernation and in others while they remained euthermic. The brain tissue from hibernating and euthermic animals was examined 3 days after implantation of microdialysis probes. Tissue response, indicated by examination of hematoxylin and eosin-stained tissue sections and immunocytochemical identification of activated microglia, astrocytes, and hemeoxygenase-1 immunoreactivity, was dramatically attenuated around probe tracks in hibernating animals compared to euthermic controls. No difference in tissue response around guide cannulae was observed between groups. Further study of the mechanisms underlying neuroprotective aspects of hibernation may lead to novel therapeutic strategies for stroke and traumatic brain injury.

Animals↗

PubMed2001

The phase-shift mutation in the glucocorticoid receptor gene: potential etiologic significance of neuroendocrine mechanisms in lupus nephritis.

BACKGROUND: Glucocorticoid (GC), a mediator of the hypothalamo-pituitary-adrenal axis, has been found to play an important role in maintaining the stability of immune endo-environment of the body. The pathogenesis of lupus nephritis, an autoimmune disease, is thought to be related to the intrinsic hyposensitivity to GC secreted by adrenal gland, and impairs the regulation of the immuno-neuro-endocrine axis. METHODS: To test this hypothesis, we examined the response of 39 clinic patients with lupus nephritis to GC and analyzed the molecular structure and function of the GC receptor (GR) on peripheral blood mononuclear cells. RESULTS: There was no difference in the level of ACTH, GC and ligand affinity of GR between the patients and the controls. The GR number on mononuclear cells of lupus patients was lower than that of the controls. There was no difference in GR number between the patients with heterogeneous response, i.e. sensitive, dependent and resistance, to GC. The analysis of exon 9 of the GC receptor with PCR-amplified single strand conformation polymorphism (PCR-SSCP) method showed the polymorphism in exon 9 of GC receptor in 8 of the 39 lupus nephritis patients. DNA sequence analysis revealed an adenine insertion at the 2439 base pair of the GC receptor gene. This phase-shift mutation caused an additional 20 amino acids being translated into protein of GC receptor. CONCLUSION: The decreased number of GC receptor and the molecular variation of GR on mononuclear cells could explain the phenomenon of GC resistance, potentially to endogenous GC, which suggested an etiological significance of neuro-endocrine-immune mechanism in lupus nephritis. This may be useful in the design of lupus nephritis therapy.

Adolescent↗

PubMed2001

The MLA6 coiled-coil, NBS-LRR protein confers AvrMla6-dependent resistance specificity to Blumeria graminis f. sp. hordei in barley and wheat.

The barley Mla locus confers multiple resistance specificities to the obligate fungal biotroph, Blumeria (= Erysiphe) graminis f. sp. hordei. Interspersed within the 240 kb Mla complex are three families of resistance gene homologs (RGHs). Probes from the Mla-RGH1 family were used to identify three classes of cDNAs. The first class is predicted to encode a full-length CC-NBS-LRR protein and the other two classes contain alternatively spliced, truncated variants. Utilizing a cosmid that contains a gene corresponding to the full-length candidate cDNA, two single-cell expression assays were used to demonstrate complementation of AvrMla6-dependent, resistance specificity to B. graminis in barley and wheat. The first of these assays was also used to substantiate previous genetic data that the Mla6 allele requires the signaling pathway component, Rar1, for function. Computational analysis of MLA6 and the Rar1-independent, MLA1 protein reveals 91.2% identity and shows that the LRR domain is subject to diversifying selection. Our findings demonstrate that highly related CC-NBS-LRR proteins encoded by alleles of the Mla locus can dictate similar powdery mildew resistance phenotypes yet still require distinct downstream signaling components.

Amino Acid Sequence↗

PubMed2001

Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers.

Previous studies have suggested that hepatitis B virus (HBV) variants may account for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)-negative patients (occult HBV infection). However, it is not known how widespread these variants are and how they influence the course of liver disease. To determine the prevalence of variants within the major hydrophilic region (MHR) of HBsAg, we investigated 2,565 subjects, including subjects with chronic hepatitis, cryptogenic cirrhosis, hemodialysis patients, and blood donors. Fifty-one of them had occult HBV infection. The entire S gene from 46 of these patients was sequenced from amplified serum HBV DNA. Forty-three percent (20 of 46) had mutations in the MHR of HBsAg. Thirty-two amino acid substitutions between positions 100-160 of the MHR of HBsAg were detected in 18 patients, and these ranged from 1 to 4 per patient. These changes involved 11 positions inside and 5 outside of the historical first and second loops of the "a" determinant, and included the following: Q101K, T115A, K122N, T123A, T126N, Q129N, G130R, T131I, M133T, F134L, C138Y, K141E, P142S, G145R, N146S, and C147F/R. Combinations of mutations were detected in 9 patients, and 7 of these have not been described before. Two further patients had insertion mutations immediately before the "a" determinant. Monoclonal antibody binding tests with the Royal Free hepatitis B surface (RFHBs) panel of antibodies revealed decreased immunoreactivity in 6 novel variants of HBsAg. The existence of patients with occult HBV infection caused by HBsAg variants, therefore, has implications for their possible transmission through sexual contact and by blood transfusion.

Alanine Transaminase↗

PubMed2001

The expression and changes of heat shock protein 70, MDA and haemorheology in rat cortex after diffuse axonal injury with secondary insults.

In the present study the role of heat shock protein 70 (HSP70) expression, changes of malonyldialdehyde (MDA) in rat cortex and haemorheology with time after diffuse axonal injury (DAI) only and DAI with secondary insults (SI) were studied. The rat DAI and DAI with SI model were made according to our previous work and animals were divided into a control and another five injury groups with time after injury. Immunohistochemical assay was used to detect the neuronal expression of HSP70 at 0.5h, 3h, 12h, 24h, 72h after DAI or DAI with SI. In the meantime, the high (etah ) and low whole blood viscosity (etaL ), haematocrit (HCT) and RBC aggregation index (AI = etaL/etah ) were also detected and calculated. MDA in the homogenised brain tissue was assayed by thiobarbituric acid (TBA) reaction. The results showed that HSP70 positive neurons were not detected at 30 minutes, but the number of HSP70 positive neurons begin to increase obviously at 3 hours, reach a peak at 24 hours (P< 0.01), and decrease at 72 hours (P= 0.05) after brain injury. The trend of expression of HSP70 was alike for both DAI only or DAI with SI. Meanwhile, MDA, etah, etaL, HCT and AI changes showed the same tendency. Compared with DAI only group, MDA and blood viscosity indexes in DAI with SI were significantly higher at respective time points (P< 0.01). It is concluded that HSP70 expression, MDA and haemorheology indices increased after brain injury and brain injury with SI. Free radicals and haemorheological changes play an important role in the aggravation of brain damage and HSP70 expression upregulation.

Animals↗

PubMed2001

Neuronal free Ca(2+)and BBB permeability and ultrastructure in head injury with secondary insult.

OBJECTIVE: To study changes in free calcium (Ca(2+)), neuronal and blood-brain barrier (BBB) permeability and ultrastructure in brain after diffuse axonal injury (DAI) with secondary brain insults (SBIs). METHOD: One hundred and twenty Sprague-Dawley (SD) rats were randomised into control, DAI alone and DAI with SBI groups which were sub-divided into 5 groups that were 0.5 h, 2 h, 12 h, 24 h, 48 h post trauma. The animal models of DAI and DAI with SBI have been described before (2). Fluorescence probe Fluo-3/Am was used to measure free Ca(2+)in neurons. Laser scan microscopy was used to detect fluorescence intensity. After the animals were anesthetized, Lanthanum nitrate liquid was used for intracardiac perfusion to assess BBB permeability. Under the transmission electron microscope, changes in cerebral ultrastructure and BBB permeability were observed. RESULTS: The fluorescence intensity was weak in the control. The concentration of free Ca(2+)in neurons was obviously increased at 30 min after brain injury, reached a peak at 12 h-24 h (P< 0.01), and appeared to decrease at 48 h after injury. In the DAI alone group, BBB tight junction opening with particles of Lanthanum nitrate outside the vessels was found at 30 min after injury, and peaked at 24 h. In DAI with SBI, the changes in ultrastructure and BBB permeability were more severe than that in the DAI alone group at the same time interval. The shape of the fluorescence concentration curve was basically the same for both kinds of brain injury. The intensity of fluorescence in DAI with SBI was higher than that in the DAI alone group at the same time interval (P< 0.05). CONCLUSION: In DAI alone and DAI with SBI, Ca(2+)overload and BBB permeability changes interact and both play important roles in the aggravation of brain damage.

Animals↗

PubMed2001

The principle of a double crystal electron interferometer.

Sinusoidal interference fringes have been observed recently using a double crystal interferometer and convergent beam electron diffraction techniques. However, the formation mechanism of the interference fringes is not understood completely. In this paper, we explain this effect using wave theory and discuss the coherence conditions necessary for this special interferometer. The excitation errors of partial exit waves leaving a crystal, which is used as a wave splitter, are found to be responsible for the formation of the interference fringes. The double crystal interferometer used in the electron diffraction manifests a new interference mechanism. Compared with two-beam interference in real space, we observe the interference effect in the reciprocal space, i.e. in the Fourier space. This effect may enable us to undertake holography in the Fraunhofer diffraction plane and measure both the phase and amplitude information of reflections. The phase information of reflections contains information on the position of atoms and the symmetry of a unit cell. Furthermore, such an interferometer has no rigorous coherence conditions.

Journal Article↗

PubMed2001

Fetal alcohol effects: mechanisms and treatment.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the "third trimester equivalent," by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.

Animals↗

PubMed2001

Cell-autonomous expression of barley Mla1 confers race-specific resistance to the powdery mildew fungus via a Rar1-independent signaling pathway.

The barley Mla locus encodes 28 characterized resistance specificities to the biotrophic fungal pathogen barley powdery mildew. We describe a single-cell transient expression assay using entire cosmid DNAs to pinpoint Mla1 within the complex 240-kb Mla locus. The MLA1 cDNA encodes a 108-kD protein containing an N-terminal coiled-coil structure, a central nucleotide binding domain, and a C-terminal leucine-rich repeat region; it also contains a second short open reading frame at the 5' end that has a possible regulatory function. Although most Mla-encoded resistance specificities require Rar1 for their function, we used the single-cell expression system to demonstrate that Mla1 triggers full resistance in the presence of the severely defective rar1-2 mutant allele. Wheat contains an ortholog of barley Mla, designated TaMla, that is tightly linked to (0.7 centimorgan) but distinct from a tested resistance specificity at the complex Pm3 locus to wheat powdery mildew. Thus, the most polymorphic powdery mildew resistance loci in barley and wheat may have evolved in parallel at two closely linked homeoloci. Barley Mla1 expressed in wheat using the single-cell transformation system failed to trigger a response to any of the wheat powdery mildew Avr genes tested, indicating that AvrMla1 is not genetically fixed in wheat mildew strains.

Alleles↗

PubMed2001

Mass/heat transfer in dimpled two-pass coolant passages with rotation.

Mass/heat transfer measurements are made in dimpled (hemispherical depressions) inlet and outlet coolant flow passages using the naphthalene sublimation method. The leading and trailing surfaces are dimpled, while the side walls are kept smooth. Measurements are made at a Reynolds number of 21,000 and for Rotation numbers of 0 and 0.2. The measurements indicate that dimples enhance surface mass/heat transfer. This enhancement is stronger in the inlet passage than in the outlet passage. Peak mass/heat transfer occurs immediately downstream of the dimples, while the minimum mass/heat transfer occurs in the dimple region itself. Higher mass/heat transfer is also observed along the lateral edges of the dimple. The location of the Sherwood number peaks suggest the existence of streamwise vortical structures generated from the leading and lateral edges of the dimples.

Journal Article↗

PubMed2001

Role of oxidative stress and thiol antioxidant enzymes in nickel toxicity and resistance in strains of the green alga Scenedesmus acutus f. alternans.

Treatment with Ni(NO3)2 leads to the formation of reactive oxygen species (ROS) in the green alga Scenedesmus acutus f. alternans, causing lipid peroxidation. This effect was stronger in a Ni-sensitive strain, UTEX72, than in a Ni-resistant strain, B4. In the resistant strain, Ni induced an increased ratio of reduced to oxidized glutathione (GSH:GSSG), whereas it caused a lowered ratio in the sensitive strain. Enzymes involved in the control of ROS were studied in these strains as well as two others that have shown different degrees of nickel resistance. The resistant strain, B4, which grows while containing large amounts of internal Ni, had much higher levels of glutathione reductase and catalase than the other strains. The sensitive strain, UTEX72, had higher levels of glutathione peroxidase, superoxide dismutase, and glucose-6-phosphate dehydrogenase than did strain B4. The resistant strains, Ni-Tol and Cu-Tol, derived from strain UTEX72, which are partly able to exclude Ni, had enzyme profiles that resembled that of UTEX72 more closely than that of B4. Treatment with 10 and 100 microM Ni for 4 or 22 h had complex effects on enzyme levels in all four strains. Ni decreased glutathione reductase in B4, slightly increased it in Ni-Tol and Cu-Tol, and did not affect the low levels of this enzyme in UTEX72. Ni lowered glutathione peroxidase in B4 and either did not affect it or slightly raised it in the other strains. Ni lowered catalase in B4 and did not affect the other strains. Superoxide dismutase was raised in B4 and Ni-Tol and lowered in Cu-Tol and UTEX72, and glucose-6-phosphate dehydrogenase was lowered in all four strains. These results suggest that one major mechanism of Ni resistance, especially in strain B4, may be the ability to combat the formation of ROS when exposed to this metal, likely by maintaining a high GSH:GSSG ratio.

Antioxidants↗

PubMed2001

Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid.

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1-50 microM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187. HOCl treatment significantly impaired both ACh- and A23187-mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to L-arginine but not D-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO3(-) and nitrite (NO2(-). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of L-arginine. These data suggest that HOCl induces endothelial dysfunction via modification of L-arginine.

Acetylcholine↗

PubMed2001

Enhanced antioxidant activity after chlorination of quercetin by hypochlorous acid.

BACKGROUND: Several epidemiological studies indicate that moderate consumption of red wine decreases both the incidence and mortality associated with cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are polyphenols present in relatively large concentrations in red wine and may play a role in this cardioprotective phenomenon. The precise mechanisms of cardioprotection remain unclear but may involve the action of these polyphenols as antioxidants, which attenuate the tissue injury that results from the production of proinflammatory oxidants such as hypochlorous acid (HOCl). METHODS: To study the interaction of these polyphenols with proinflammatory oxidants, we mixed quercetin or rutin with HOCl (0-150 microM) and analyzed the reaction products by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. RESULTS: Stable mono- and dichlorinated derivates were detected for both quercetin and the glycoside derivative, rutin, which suggests that both the conjugated and unconjugated forms of quercetin reacted with HOCl similarly. Chlorination of quercetin occurred only at two sites, and the derivates (6-chloroquercetin, 6,8-dichloroquercetin) were more potent antioxidants toward oxidative modification of low-density lipoproteins and ABTS radical formation than the unmodified form. CONCLUSIONS: These data suggest that under certain pathological conditions in vivo (e.g., inflammation), flavonols may be converted to chlorinated derivates, which exhibit an enhanced antioxidant potential and thereby play a role in cardioprotection.

Analysis of Variance↗

PubMed2001

In vivo delivery of antisense oligonucleotides in pH-sensitive liposomes inhibits lipopolysaccharide-induced production of tumor necrosis factor-alpha in rats.

Kupffer cells play an important role in the pathogenesis of liver diseases. During endotoxemia and alcohol-induced liver disease, tissue injury is preceded by an excessive release of cytokines by these macrophages. Tumor necrosis factor-alpha (TNF-alpha) is one of the key cytokines associated with liver injury. Pre-exposure of animals to TNF-alpha antibodies has been shown to prevent macrophage-mediated liver injury in experimental animals. In this article, we describe a method to encapsulate in pH-sensitive liposomes and to deliver an antisense phosphorothioate oligonucleotide (TJU-2755) against TNF-alpha. We describe the efficacy of this formulation in inhibiting endotoxin-mediated production of TNF-alpha. The liposomes prepared were stable for over 4 weeks at pH 7.4, but readily released their contents when exposed to an acidic environment below pH 6, similar to the pH that exists in early endosomes. Male Sprague-Dawley rats were administered (i.v.) liposome-encapsulated TJU-2755 (1-2 mg/kg body wt.). Empty liposomes served as controls. Forty-eight hours postinjection, the animals were administered a single dose of lipopolysaccharide (50 microg/kg body wt.) and were sacrificed 90 min later. The TNF-alpha produced by excised liver incubated ex vivo and the levels of plasma TNF-alpha were determined. After a single administration of liposome-encapsulated antisense TJU-2755, a 30% reduction in TNF-alpha produced by liver slices was observed. Two daily doses of the antisense oligonucleotide inhibited TNF-alpha production by 50%. This was associated with a 65 to 70% reduction in plasma levels of TNF-alpha, compared with controls. These results indicate that oligonucleotide TJU-2755 encapsulated in pH-sensitive liposomes can be used to effectively reduce endotoxin-mediated production of TNF-alpha in macrophages in vivo and thus may be of value in attenuating or preventing macrophage-mediated liver injury.

Animals↗