Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats.

BACKGROUND/AIM: Disability and mortality rates for renal failure are still increasing. DNA damage and oxidative stress intoxication from body metabolism, high blood glucose, or the environment cause significant kidney damage. Recently, we reported that Box A of HMGB1 (Box A) acts as molecular scissors, producing DNA gaps that prevent DNA damage in kidney cell lines and ultimately reverse aging phenotypes in aging rat models. The present study aimed to demonstrate the potency of Box A in preventing D-galactose (D-gal)-induced kidney injury. MATERIALS AND METHODS: A Box A expression plasmid was constructed and administered to a rat model. D-gal was injected subcutaneously for eight weeks. Serum was collected to study renal function, and white blood cells were collected for DNA gap measurement. Kidney tissue was also collected for γ-H2AX and NF-κB immunostaining; Senescence-associated (SA)-beta-gal staining; and analysis of the mRNA expression of p16INK4A, TNF-α, and IL-6. Moreover, histopathology analysis was performed using hematoxylin & eosin and Masson trichome staining. RESULTS: Pretreatment with Box A administration prevented the reduction of DNA gaps and the consequences of the DNA damage response, which include elevated serum creatinine; high serum BUN; an increased positive SA-beta-gal staining area; overexpression of p16INK4A, NF-κB and senescence-associated secretory phenotype molecules, including IL-6, TNF-α; and histological alterations, including tubular dilation and collagen accumulation. CONCLUSION: Box A effectively prevents DNA gap reduction and all D-gal-induced kidney pathological changes at the molecular, histological, and physiological levels. Therefore, Box A administration is a promising novel therapeutic strategy to prevent DNA-damaging agent-induced kidney failure.

Effects of quercetin and extracts from Phyllanthus emblica, Morus alba, and Ginkgo biloba on platelet recovery in a rat model of chemotherapy-induced thrombocytopenia.

Background: Chemotherapy-induced thrombocytopenia (CIT) is a major reason for chemotherapy delays, dose reduction, or even treatment discontinuation, which may impact oncologic outcomes. We investigated the effects of quercetin and extracts of Phyllanthus emblica fruit (PEE), Morus alba leaf (MAE), and Ginkgo biloba leaf (GBE) on platelet recovery in a rat model of chemotherapy-induced thrombocytopenia. Methods: The total phenolic content (TPC), total flavonoid content (TFC), quercetin content, and antioxidant activities of all the extracts were determined. Sixty male Sprague Dawley rats were categorized into healthy controls and CIT groups. The CIT groups was administered a cyclophosphamide solution, while the control group received a saline solution. Each group was then subdivided into five subgroups of six animals which were administered with PEE, MAE, GBE, quercetin, or a vehicle for 15 days. Results: The highest quercetin content was found in PEE, followed by MAE and GBE, which correlated with their antioxidant properties. Administration of these extracts and quercetin did not significantly change the platelet counts in healthy rats. Thrombocytopenic rats treated with PEE, MAE, and GBE also were not associated with significant changes in platelet counts. However, more rapid platelet count recovery was observed in all groups receiving extracts. On day 11, platelet counts in the PEE, MAE, and GBE groups returned to near baseline levels with a mean of 4.29 %, -40.77 %, and -14.24 %, respectively, compared to -71 % in the CIT group. In thrombocytopenic rats treated with quercetin, there was a significant increase in platelet counts on days 9 and 11, with a mean decrease of 5.41 % from baseline on day 11. Conclusion: Quercetin improved platelet recovery in the animal model of CIT. This finding merits for further investigation to better elucidate the health benefits of quercetin and quercetin-rich plants and potential pharmacokinetics underpinning their activity in thrombocytopenia.

Exercise and Caloric Restriction Exert Different Benefits on Skeletal Muscle Metabolism in Aging Condition.

Exercise and caloric restriction improve skeletal muscle metabolism. However, the benefits of exercise and caloric restriction on skeletal muscle metabolism in aging have never been compared. Seven-week-old male Wistar rats (n = 24) were divided into 4 groups (n = 6 per group) to receive either normal saline solution for 28 weeks, 150 mg/kg/day of D-galactose for 28 weeks to induce premature aging, 150 mg/kg/day of D-galactose for 28 weeks plus exercise for 16 weeks (week 13-28), or 150 mg/kg/day of D-galactose for 28 weeks plus 30% caloric restriction for 16 weeks (week 13-28). The 17-month-old rats (n = 6) were also injected with normal saline solution for 28 weeks as the naturally aged controls. At the end of week 28, total walking distance and fatty acid and carbohydrate oxidation during physical activity were determined. Then, all rats were euthanized for the collection of blood and tibialis anterior muscle. The results showed that D-galactose successfully mimicked the natural aging of skeletal muscle. Exercise and caloric restriction equally improved carbohydrate oxidation during physical activity and myogenesis. However, exercise was superior to caloric restriction in terms of improving fatty acid oxidation and oxidative phosphorylation. Interestingly, caloric restriction decreased oxidative stress, whereas exercise increased oxidative stress of skeletal muscle. All of these findings indicated that the benefits of exercise and caloric restriction on skeletal muscle metabolism during aging were different, and therefore the combination of exercise and caloric restriction might provide greater efficacy in ameliorating skeletal muscle aging.

Cyclosorus Terminans Extract Alleviates Neuroinflammation in Insulin Resistant Rats.

High-fat diet consumption for an extended period causes obesity, systemic metabolic disturbance, and brain insulin resistance, resulting in neuroinflammation. Although the beneficial effect of Cyclosorus terminans extract on obesity-related insulin resistance has been demonstrated, little is known about how it affects neuroinflammation and brain insulin resistance in obese rats. Male Wistar rats were given either a normal diet (ND, n = 6) or a high-fat diet (HFD, n = 24) for a total of 14 weeks. At the beginning of the week, 13 rats in the ND group were given vehicle orally for 2 weeks, while rats on HFD diets were randomized to one of four groups and given either vehicle, 100 mg/kg/day of Cyclosorus terminans extract, 200 mg/kg/day of Cyclosorus terminans extract, or 20 mg/kg/day of pioglitazone orally for 2 weeks. After the experimental period, blood and brain samples were taken to assess metabolic and brain parameters. HFD-fed rats had obesity, systemic and brain insulin resistance, brain inflammation, microglial and astrocyte hyperactivity, and brain necroptosis. Treatment with 200 mg/kg/day of Cyclosorus terminans extract and pioglitazone equally attenuated obesity, insulin resistance, brain insulin dysfunction, and neuroinflammation in insulin resistant rats. Our findings suggest that Cyclosorus terminans extract may hold promise as a therapeutic agent for insulin resistance and neuroinflammation in obese conditions.

Long-term lifestyle intervention is superior to transient modification for neuroprotection in D-galactose-induced aging rats.

AIMS: To investigate whether transient dietary restriction or aerobic exercise in young adulthood exert long-lasting protection against brain aging later in life. MAIN METHODS: Seven-week-old male Wistar rats were divided into 2 groups and given either normal saline as a vehicle (n = 8) or 150 mg/kg/day of D-galactose (n = 40) for 28 weeks, the D-galactose being used to induce aging. At week 13 of the experiment, D-galactose-treated rats were further divided into 5 groups, 1) no intervention, 2) transient dietary restriction for 6 weeks (week 13-18), 3) transient exercise for 6 weeks (week 13-18), 4) long-term dietary restriction for 16 weeks (week 13-28), and 5) long-term exercise for 16 weeks (week 13-28). At the end of week 28, cognitive function was examined, followed by molecular studies in the hippocampus. KEY FINDINGS: Our results showed that either long-term dietary restriction or aerobic exercise effectively attenuated cognitive function in D-galactose-treated rats via the attenuation of oxidative stress, cellular senescence, Alzheimer's-like pathology, neuroinflammation, and improvements in mitochondria, brain metabolism, adult neurogenesis, and synaptic integrity. Although transient interventions provided benefits in some brain parameters in D-galactose-treated rats, an improvement in cognitive function was not observed. SIGNIFICANCE: Our findings suggested that transient lifestyle interventions failed to exert a long-lasting protective effect against brain aging. Hence, novel drugs mimicking the neuroprotective effect of long-term dietary restriction or exercise and the combination of the two since young age appear to be more appropriate treatments for the elderly who are unable to engage in long-term dietary restriction or exercise.

Melatonin Reduces Aggravation of Renal Ischemia-Reperfusion Injury in Obese Rats by Maintaining Mitochondrial Homeostasis and Integrity through AMPK/PGC-1α/SIRT3/SOD2 Activation.

This study examined the potential benefits of melatonin against renal ischemia and reperfusion (IR) injury in obesity and explored the underlying mechanisms. Obesity was induced in Wistar rats by feeding a high-fat diet for 16 weeks. Three obese groups that underwent renal IR induction (30-min renal ischemia followed by 24-h reperfusion) were randomly assigned to receive melatonin at ischemic onset, reperfusion onset, or pretreatment for 4 weeks before IR induction. Groups of vehicle-treated obese and normal-diet-fed rats that underwent sham or IR induction were also included in the study. The results showed that renal functional and structural impairments after IR incidence were aggravated in obese rats compared to normal-diet-fed rats. The obese-IR rats also exhibited oxidative stress, mitochondrial dysfunction, apoptosis, and mitochondrial dynamics and mitophagy imbalances, which were all considerably improved upon melatonin treatment, irrespective of the treatment time. This study suggests the prophylactic and therapeutic efficacy of melatonin in IR-induced acute kidney injury (AKI) in obese individuals, which may improve the prognosis of AKI in these populations. The benefits of melatonin are likely mediated by the modification of various signaling molecules within the mitochondria that maintain mitochondrial redox balance and lead to the protection of mitochondrial homeostasis and integrity.

Ferroptosis inhibitor improves cardiac function more effectively than inhibitors of apoptosis and necroptosis through cardiac mitochondrial protection in rats with iron-overloaded cardiomyopathy.

Iron overload cardiomyopathy (IOC) is the leading cause of death in cases of iron overload in patients. Previous studies demonstrated that iron overload led to cardiomyocyte dysfunction and death through multiple pathways including apoptosis, necroptosis and ferroptosis. However, the dominant cell death pathway in the iron-overloaded heart needs clarification. We tested the hypothesis that ferroptosis, an iron-dependent cell death, plays a dominant role in IOC, and ferroptosis inhibitor exerts greater efficacy than inhibitors of apoptosis and necroptosis on improving cardiac function in iron-overloaded rats. Iron dextran was injected intraperitoneally into male Wistar rats for four weeks to induce iron overload. Then, the rats were divided into 5 groups: treated with vehicle, apoptosis inhibitor (z-VAD-FMK), necroptosis inhibitor (Necrostatin-1), ferroptosis inhibitor (Ferrostatin-1) or iron chelator (deferoxamine) for 2 weeks. Cardiac function, mitochondrial function, apoptosis, necroptosis and ferroptosis were determined. The increased expression of apoptosis-, necroptosis- and ferroptosis-related proteins, were associated with impaired cardiac and mitochondrial function in iron-overloaded rats. All cell death inhibitors attenuated cardiac apoptosis, necroptosis and ferroptosis in iron-overloaded rats. Ferrostatin-1 was more effective than the other drugs in diminishing mitochondrial dysfunction and Bax/Bcl-2 ratio. Moreover, both Ferrostatin-1 and deferoxamine reversed iron overload-induced cardiac dysfunction as indicated by restored left ventricular ejection fraction and E/A ratio, whereas z-VAD-FMK and Necrostatin-1 only partially improved this parameter. These results indicated that ferroptosis could be the predominant form of cardiomyocyte death in IOC, and that inhibiting ferroptosis might be a potential novel treatment for IOC.

In vitro susceptibility to miltefosine of amphotericin B-resistant Leishmania (Mundinia) martiniquensis.

Leishmania (Mundinia) martiniquensis is a newly described species that causes human visceral, disseminated, and mucocutaneous leishmaniases. Amphotericin B deoxycholate (AmpB) is the first-line drug for the treatment of leishmaniasis in Thailand; however, several relapse cases of leishmaniasis caused by L. martiniquensis have been documented. In this study, in vitro susceptibility to AmpB and miltefosine (MIL) of wild-type (before treatment, LSCM1) and two AmpB-resistant L. martiniquensis strains (an in vitro-induced AmpB-resistant strain, AmpBRP2i, and a relapse strain, LSCM1-6) were determined. Results reveal that the IC50 value and resistance index against both drugs of promastigotes and intracellular amastigotes of the AmpBRP2i and LSCM1-6 strains were statistically significantly higher than those of the LSCM1 strain suggesting that cross-resistance with MIL occurred in both AmpB-resistant strains. The results of this study advocate further investigation into mechanisms that involve the complex nature of AmpB/MIL resistance in L. martiniquensis and development of effective methods for the identification of the AmpB-resistant parasites to help delivery of appropriate treatments for patients and for epidemiological surveys to survey the potential spread of drug-resistant strains.

Titanium Dioxide Nano-Formulation: Characterization, Antimicrobial Activity, and Wound Healing in Animals.

The use of metal oxide nanoparticles as an alternative antimicrobial agent has gained attention due to the increasing problem of antimicrobial resistance. Understanding its properties and potential benefits can contribute to the development of more effective and sustainable treatments in veterinary medicine. The aim of this study was to characterize TiO2-NP formulations and evaluate their antibacterial and wound healing abilities. The diameters and zeta potentials were determined using the Zetasizer in conjunction with dynamic light scattering. The agar-well diffusion method, time-kill kinetic assay and crystal violet assay were used to evaluate their antimicrobial activities. Wound healing assays were conducted both in vitro and in vivo. The study demonstrated that TiO2-NP formulations exhibit significant antimicrobial properties against various bacterial strains such as S. aureus and E. coli. No measurable E. coli growth was observed within a 15-min period following exposure to TiO2-NP formulations. The TiO2-NP formation can improve wound healing by enhancing cell migration and collagen formation in both in vitro and in vivo conditions. In summary, our study suggests that TiO2-NP has the potential for use as an antimicrobial agent for animal wound treatment due to its ability to suppress bacterial growth and biofilm formation, as well as to enhance wound healing.

Chronic D-galactose administration induces natural aging characteristics, in rat's brain and heart.

We aimed to investigate the effect of chronic D-galactose exposure on the mimicking of natural aging processes based upon the hallmarks of aging. Seven-week-old male Wistar rats (n = 12) were randomly assigned to receive either normal saline solution as a vehicle (n = 6) or 150 mg/kg/day of D-galactose subcutaneously for 28 weeks. Seventeen-month-old rats (n = 6) were also included as the chronologically aged controls. At the end of week 28 of the experiment (when the rats reach 35 weeks old and 24 months old), all rats were sacrificed for brain and heart collection. Our results showed that chronic D-galactose exposure mimicked natural aging characteristics of the brain and the heart in terms of deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, and functional impairment. All of which highlight the potential of D-galactose as a substance for inducing brain and cardiac aging in animal experiments.

Amphotericin B resistance correlates with increased fitness in vitro and in vivo in Leishmania (Mundinia) martiniquensis.

Amphotericin B (AmpB) deoxycholate is the available first-line drug used to treat visceral leishmaniasis caused by Leishmania (Mundinia) martiniquensis, however, some cases of AmpB treatment failure have been reported in Thailand. Resistance to drugs is known to affect parasite fitness with a potential impact on parasite transmission but still little is known about the effect of resistance to drugs on L. martiniquensis. Here we aimed to gain insight into the fitness changes occurring after treatment failure or in vitro-induced resistance to AmpB. L. martiniquensis parasites isolated from a patient before (LSCM1) and after relapse (LSCM1-6) were compared for in vitro and in vivo fitness changes together with an in vitro induced AmpB-resistant parasite generated from LSCM1 parasites (AmpBRP2i). Results revealed increased metacyclogenesis of the AmpBPR2i and LSCM1-6 strains (AmpB-resistant strains) compared to the LSCM1 strain and increased fitness with respect to growth and infectivity. The LSCM1-6 and AmpBRP2i strains were present in mice for longer periods compared to the LSCM1 strain, but no clinical signs of the disease were observed. These results suggest that the AmpB-resistant parasites could be more efficiently transmitted to humans and maintained in asymptomatic hosts longer than the susceptible strain. The asymptomatic hosts therefore may represent "reservoirs" for the resistant parasites enhancing transmission. The results in this study advocate an urgent need to search and monitor for AmpB-resistant L. martiniquensis in patients with relapsing leishmaniasis and in asymptomatic patients, especially, in HIV/Leishmania coinfected patients.

Ferrostatin-1 and Z-VAD-FMK potentially attenuated Iron-mediated neurotoxicity and rescued cognitive function in Iron-overloaded rats.

AIMS: The present study was aimed to investigate the effects of cell death inhibitors including ferroptosis inhibitor, ferrostatin-1 (FER-1) and a pan-caspase inhibitor, z-VAD-FMK on brain parameters and cognitive function in iron-overloaded rats. MAIN METHODS: Male Wistar rats (n = 30) were divided into 2 groups to receive an intraperitoneal injection with either 10 % dextrose in normal saline solution (NSS) (control group, n = 6) or 100 mg/kg iron dextran (Fe group, n = 24) for 6 weeks. After 4 weeks of injection, Fe-injected rats were subdivided into 4 subgroups (n = 6/subgroup) to subcutaneously receive with 1) vehicle (10 % DMSO in NSS), 2) deferoxamine (25 mg/kg), 3) FER-1 (2 mg/kg), or 4) z-VAD-FMK (1 mg/kg). Control group was received vehicle. All subgroups were received each treatment for 2 weeks. Behavioral tests including the Morris water maze test and novel object recognition test, were performed at the end of treatment. Then, circulating iron levels and brain parameters including blood-brain barrier proteins, iron level, synaptic proteins, and ferroptosis/apoptosis were determined. KEY FINDINGS: All treatment attenuated iron-overloaded condition, brain pathologies, and the cognitive impairment. FER-1 and z-VAD-FMK provided superior effects than deferoxamine by attenuating loss of synaptic proteins and restoring cognitive function in both hippocampal-dependent and hippocampal-independent manners. SIGNIFICANCE: These findings suggest that cell death inhibitors act as the novel therapeutic targets for neuroprotection in iron-overloaded condition.

Cyclosorus terminans Extract Ameliorates Insulin Resistance and Non-Alcoholic Fatty Liver Disease (NAFLD) in High-Fat Diet (HFD)-Induced Obese Rats.

Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.

The roles of HMGB1-produced DNA gaps in DNA protection and aging biomarker reversal.

The endogenous DNA damage triggering an aging progression in the elderly is prevented in the youth, probably by naturally occurring DNA gaps. Decreased DNA gaps are found during chronological aging in yeast. So we named the gaps "Youth-DNA-GAPs." The gaps are hidden by histone deacetylation to prevent DNA break response and were also reduced in cells lacking either the high-mobility group box (HMGB) or the NAD-dependent histone deacetylase, SIR2. A reduction in DNA gaps results in shearing DNA strands and decreasing cell viability. Here, we show the roles of DNA gaps in genomic stability and aging prevention in mammals. The number of Youth-DNA-GAPs were low in senescent cells, two aging rat models, and the elderly. Box A domain of HMGB1 acts as molecular scissors in producing DNA gaps. Increased gaps consolidated DNA durability, leading to DNA protection and improved aging features in senescent cells and two aging rat models similar to those of young organisms. Like the naturally occurring Youth-DNA-GAPs, Box A-produced DNA gaps avoided DNA double-strand break response by histone deacetylation and SIRT1, a Sir2 homolog. In conclusion, Youth-DNA-GAPs are a biomarker determining the DNA aging stage (young/old). Box A-produced DNA gaps ultimately reverse aging features. Therefore, DNA gap formation is a potential strategy to monitor and treat aging-associated diseases.

Perilla Seed Oil Alleviates Gut Dysbiosis, Intestinal Inflammation and Metabolic Disturbance in Obese-Insulin-Resistant Rats.

BACKGROUND: High-fat diet (HFD) consumption induced gut dysbiosis, inflammation, obese-insulin resistance. Perilla seed oil (PSO) is a rich source of omega-3 polyunsaturated fatty acids with health promotional effects. However, the effects of PSO on gut microbiota/inflammation and metabolic disturbance in HFD-induced obesity have not been investigated. Therefore, we aimed to compare the effects of different doses of PSO and metformin on gut microbiota/inflammation, and metabolic parameters in HFD-fed rats. METHODS: Thirty-six male Wistar rats were fed either a normal diet or an HFD for 24 weeks. At week 13, HFD-fed rats received either 50, 100, and 500 mg/kg/day of PSO or 300 mg/kg/day metformin for 12 weeks. After 24 weeks, the metabolic parameters, gut microbiota, gut barrier, inflammation, and oxidative stress were determined. RESULTS: HFD-fed rats showed gut dysbiosis, gut barrier disruption with inflammation, increased oxidative stress, metabolic endotoxemia, and insulin resistance. Treatment with PSO and metformin not only effectively attenuated gut dysbiosis, but also improved gut barrier integrity and decreased gut inflammation. PSO also decreased oxidative stress, metabolic endotoxemia, and insulin resistance in HFD-fed rats. Metformin had greater benefits than PSO. CONCLUSION: PSO and metformin had the beneficial effect on attenuating gut inflammation and metabolic disturbance in obese-insulin resistance.

Capsaicinoid nonivamide improves nonalcoholic fatty liver disease in rats fed a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is a chronic disease that causes morbidity associated with metabolic syndrome. NAFLD is a worldwide problem and represents a major cause of liver injury, which can lead to liver cell death. We investigated the effects of nonivamide (pelargonic acid vanillylamide, PAVA; 1 mg/kg) and rosuvastatin (RSV; 10 mg/kg) on hepatic steatosis induced by a high-fat diet (HFD). Male Sprague-Dawley rats were fed a HFD for 16 weeks then received PAVA or RSV for 4 additional weeks. We examined the metabolic parameters, function, fat content, histological alterations, reactive oxygen species production, and apoptotic cell death of the liver, in addition to the expression of the following important molecules: transient receptor potential cation channel subfamily V member 1 (TRPV1) phosphorylation of sterol regulatory element binding protein (pSREBP-1c/SREBP-1c), total and membrane glucose transporter 2 (GLUT2), 4-hydroxynonenal (4-HNE), and cleaved caspase-3. HFD-induced hepatic steatosis was associated with significantly increased morphological disorganization, injury markers, oxidative stress, lipid peroxidation, and apoptosis. However, metabolic dysfunction and hepatic injury were reduced by RSV and PAVA treatment. PAVA regulated lipid deposition, improved insulin resistance, and decreased oxidative stress and apoptotic cell death. Therefore, PAVA represents a promising therapeutic approach for treating metabolic disorders in patients with NAFLD.

Effects of dapagliflozin and statins attenuate renal injury and liver steatosis in high-fat/high-fructose diet-induced insulin resistant rats.

High-fat high-fructose diet (HFF) in obesity can induce dyslipidemia and lipid accumulation both in kidney and liver which related to insulin resistance and lipotoxicity-induced cellular damage. We investigated whether dapagliflozin with or without atorvastatin could improve lipid accumulation-induced kidney and liver injury in HFF-induced insulin resistant rats. Male Wistar rats were fed with HFF for 16 weeks and then received drug treatments for 4 weeks; vehicle, dapagliflozin, atorvastatin and dapagliflozin plus atorvastatin treatment groups. HFF rats demonstrated insulin resistance, dyslipidemia, liver injury and renal dysfunction associated with impaired renal lipid metabolism and lipid accumulation. Dapagliflozin and combination treatment could improve HFF-induced insulin resistance, lipogenesis and lipotoxicity-related renal oxidative stress, inflammation, fibrosis and apoptosis leading to kidney dysfunction recovery. Liver injury-associated inflammation was also improved by these two regimens. Notably, the reduced lipid accumulation in liver and kidney that linked to an improvement of lipid oxidation was prominent in the combination treatment. Therefore, dapagliflozin combined with atorvastatin treatment exert the beneficial effects on lipid metabolism and lipotoxicity in liver and kidney injury via the attenuation of oxidative stress, fibrosis and apoptosis in insulin resistant model.

Molecular epidemiology and characterization of porcine adenoviruses in pigs with diarrhea in Thailand.

Pigs have been assumed as a source of human viral infections. Surveillance of viruses in animals is essential to evaluate the risk to human and animal health and to determine economic impact. A number of studies focused mainly on well- known enteritis viruses such as porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine group A rotavirus (PRVA), however, little data is available for porcine adenovirus (PAdV). In this study, the presence of PAdV was investigated in fecal samples collected from piglets with and without diarrhea from 31 commercial pig farms in northern Thailand. A total of 781 fecal specimens (516 from diarrheic piglets and 265 from non-diarrheic piglets) were screened for adenovirus using nested-PCR. Initial screening both in diarrheic and non-diarrheic piglets showed the overall prevalence of PAdV infection in piglets at 16.9% (132/781). Co-infection with PRVA was found in 24 out of 132 (18.2%) PAdV positive cases whereas PAdV mono-infection was observed at 81.8% (108/132). The prevalence of PAdV infection in diarrheic piglets (24.2%, 102/516) was significantly higher than those detected in non-diarrheic piglets (2.6%, 7/265). Most of PAdV detected in this study (97%, 128/132) were genotype 3 while the other 4 PAdV positive samples were non identifiable genotype. Phylogenetic analysis revealed that the viruses detected in diarrheic and non-diarrheic piglets displayed a closely related (95.4 to 100%) nucleotide sequence identity. To our knowledge, this is the first report on the epidemiology and molecular characterization of PAdV in piglets in Thailand.

Detection and genetic characterization of porcine astroviruses in piglets with and without diarrhea in Thailand.

Porcine astrovirus (PAstV) is widely distributed and highly prevalent among pigs, nevertheless its clinical significance remains unclear as it can be detected in both diarrheic and in healthy pigs. Information about the prevalence, clinical significance and molecular characterization of PAstV in Thailand is not available. This study investigated the prevalence of PAstV in 488 fecal samples collected from piglets with and without diarrhea in 28 pig farms in northern and central parts of Thailand using RT-PCR. The overall prevalence of PAstV infection was 6.5% (32/488), of which 21/251 (8.4%) were in diarrheic and 11/237 (4.6%) were in healthy pigs. Of 32 positive samples, 46.9% were positive for PAstV alone whereas 53.1% were co-infected with porcine group A rotavirus (PRVA). A phylogenetic analysis of the partial RNA-dependent RNA polymerase/capsid genes revealed two lineages of PAstV strains detected in this study. PAstV4 was the most dominant genotype (92%), followed by PAstV2 (8%). This study revealed for the first time that PAstV4 and PAstV2 were circulating in Thailand with PAstV4 as the most dominant genotype in pig herds in northern and central parts of Thailand.

Postoperative Pericardial Adhesion Prevention Using Collagen Membrane in Pigs: A Pilot Study.

OBJECTIVE: The operating procedure of a resternotomy in open-heart surgery is a complicated procedure with potentially problematic outcomes partly due to potential adhesions in the pericardial cavity and retrosternal space. Use of a collagen membrane has shown encouraging results in adhesion prevention in several regions of the body. This study was designed to evaluate the effectiveness of the use of this collagen membrane in the prevention of pericardial adhesions. MATERIALS AND METHODS: A total of 12 pigs were divided randomly into 2 groups: an experimental group in which collagen membranes were used and a control group. After sternotomy and an anterior pericardiectomy, the epicardial surface was exposed to room air and irrigated with saline, and an epicardial abrasion was performed using a sponge. The pericardial defect was repaired using a collagen membrane in the experimental group or left uncovered in the control group. After 8 to 12 weeks, the pigs were killed, and a resternotomy was performed by a single-blinded surgeon enabling the evaluation of adhesions. The heart was then removed and sent for microscopic assessment conducted by a single-blinded pathologist. RESULTS: The resternotomy operations performed using a collagen membrane demonstrated a nonstatistically significant trend of fewer macroscopic and microscopic adhesions in all regions (P > .05), particularly in the retrosternal and defect regions. CONCLUSIONS: This study showed nonstatistically significant differences between the outcomes in the collagen membrane group and the control group in both macroscopic and microscopic adhesion prevention. Due to the many limitations in animal study design, further studies in human models will be needed before the true value of this procedure can be evaluated.