The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development.

Selection of Highly Specific DNA Aptamer for the Development of QCM-Based Arsenic Sensor.

Heavy metal arsenic is a water pollutant that affects millions of lives worldwide. A novel aptamer candidate for specific and sensitive arsenic detection was identified using Graphene Oxide-SELEX (GO-SELEX). Eleven rounds of GO-SELEX were performed to screen As(III) specific sequences. The selected aptamer sequences were evaluated for their binding affinity. The dissociation constant of the best aptamer candidate, As-06 was estimated by fluorescence recovery upon target addition, and it was found to be 8.15 nM. A QCM-based biosensing platform was designed based on the target-triggered release of aptamer from the QCM electrode. An rGO-SWCNT nanocomposite was adsorbed on the gold surface, and the single-stranded probe was stacked on the rGO-CNT layer. Upon addition of the target to the solution, a concentration-dependent release of the ssDNA probe was observed and recorded as the change in the electrode frequency. The developed QCM sensor showed a dynamic linear range from 10 nM to 100 nM and a low detection limit of 8.6 nM. The sensor exhibited excellent selectivity when challenged with common interfering anions and cations.

Development of fluorescent aptasensor for detection of acephate by utilizing graphene oxide platform.

A fluorescent graphene oxide based aptasensing platform was developed for the detection of acephate. The aptamers specific to the acephate were screened through GO-SELEX (Graphene Oxide - Systematic Evolution of Ligands by EXponential enrichment) method for six rounds. The screened aptamers were analyzed for their binding affinity and specificity by using fluorescence-based assay. The aptamer AAPT3 that demonstrated highest affinity (Kd = 9 ± 1 nM) and an excellent selectivity, was employed in the development of fluorescent aptasensor. Under optimal conditions, the aptasensor showed low limit of detection (4 ng mL-1) and a wide dynamic linear range (5-80 ng mL-1). The aptasensor was also validated against water samples spiked with acephate, which showed fluorescence recovery from 94 to 107% and coefficient of variation 1-5%. These results indicate that the developed aptasensor can be used for sensitive, selective, and accurate detection of acephate in various samples.

Arsenic Resistance Mechanisms in Pseudomonas mendocina SMSKVR-3 Strain Isolated from Khetri Copper Mines, Rajasthan, India.

An arsenic resistant bacteria SMSKVR-3 has been isolated from the rhizospheric soil of the metal-contaminated site of khetri copper mines situated in the Jhunjhunu district of Rajasthan, India. The strain showed homology with Pseudomonas mendocina strain ATCC 25411. This gram-negative isolate exhibited optimal growth in M9 minimal media with temperature and salt concentration as 30 °C and 0.25% (w/v), respectively, at pH 7.0. The similar growth pattern and SEM analysis of this strain exposed to M9 minimal media alone, M9 media supplemented with 300 mM arsenate [As(V)] or M9 media supplemented with 1.34 mM arsenite [As(III)] indicate the existence of the strong arsenic resistance mechanism. The isolate was able to produce siderophores and was able to reduce As(V) to As(III). A decrease in polyP concentration from 354.8 µg/1010 CFU mL-1 at 0 h to 0.043 µg/1010 CFU mL-1 at 8 h incubation with As(V) was in correlation with the change in intracellular As(V) concentration (116.98 mg L-1/1010 cells at 0 h to 88.65 mg L-1/1010 at 8 h) with time. This shows the possible role of polyP bodies in the regulation of As(V) concentration inside the cell. The presence of arsC gene in P.mendocina SMSKVR-3 was confirmed by the PCR amplification of arsC gene. The BLAST analysis of the sequenced gene represented 98.59% identity with the P. mendocina S5.2 arsenate reductase. These results indicate that the observed arsenic resistance in SMSKVR-3 is due to a combination of siderophore production, the transformation of As(V) to As(III) by arsenate reductase, multi-drug efflux pump, and polyP bodies mediated metal resistance mechanism.

A 12-week aerobic exercise intervention results in improved metabolic function and lower adipose tissue and ectopic fat in high-fat diet fed rats.

Investigations of long-term exercise interventions in humans to reverse obesity is expensive and is hampered by poor compliance and confounders. In the present study, we investigated intrahepatic and muscle fat, visceral and subcutaneous fat pads, plasma metabolic profile and skeletal muscle inflammatory markers in response to 12-week aerobic exercise in an obese rodent model. Six-week-old male Wistar rats (n=20) were randomized to chow-fed control (Control, n=5), sedentary high-fat diet (HFD, n=5), chow-fed exercise (Exercise, n=5) and HFD-fed exercise (HFD+Exercise, n=5) groups. The exercise groups were subjected to 12 weeks of motorized treadmill running at a speed of 18 m/min for 30 min/day. Differences in post-intervention measures were assessed by analysis of covariance (ANCOVA), adjusted for baseline bodyweight and pre-intervention measures, where available. Post-hoc analyses were performed with Bonferroni correction. Plasma metabolic profile was worsened and fat pads, ectopic fat in muscle and liver and inflammatory markers in skeletal muscle were elevated in sedentary HFD-fed animals relative to chow-fed controls. HFD+Exercise animals had significantly lower leptin (P=0.0004), triglycerides (P=0.007), homeostatic model assessment of insulin resistance (HOMA-IR; P=0.065), intramyocellular lipids (IMCLs; P=0.003), intrahepatic lipids (IHLs; P<0.0001), body fat% (P=0.001), subcutaneous adipose tissue (SAT; P<0.0001), visceral adipose (P<0.0001) and total fat mass (P<0.0001), relative to sedentary HFD-fed animals, despite only modestly lower bodyweight. Messenger RNA (mRNA) expression of inflammatory markers Interleukin 6 (IL6) and Tumor necrosis factor α (TNFα) were also reduced with aerobic exercise in skeletal muscle. Our results suggest that 12 weeks of aerobic exercise training is effective in improving metabolic health, fat depots, ectopic fat and inflammation even against a high-fat dietary background.

Dynamic contrast-enhanced MRI of brown and beige adipose tissues.

PURPOSE: The vascular blood flow in brown adipose tissue (BAT) is important for handling triglyceride clearance, increased blood flow and oxygenation. We used dynamic contrast-enhanced (DCE)-MRI and fat fraction (FF) imaging for investigating vascular perfusion kinetics in brown and beige adipose tissues with cold exposure or treatment with ß3-adrenergic agonist. METHODS: FF imaging and DCE-MRI using gadolinium-diethylenetriaminepentaacetic acid were performed in interscapular BAT (iBAT) and beige tissues using male Wister rats (n = 38). Imaging was performed at thermoneutral condition and with either cold exposure, treatment with pharmacological agent CL-316,243, or saline. DCE-MRI and FF data were co-registered to enhance the understanding of metabolic activity. RESULTS: Uptake of contrast agent in activated iBAT and beige tissues were significantly (P < .05) higher than nonactivated iBAT. The Ktrans and kep increased significantly in iBAT and beige tissues after treatment with either cold exposure or ß3-adrenergic agonist. The FF decreased in activated iBAT and beige tissues. The Ktrans and FF from iBAT and beige tissues were inversely correlated (r = 0.97; r = 0.94). Significant increase in vascular endothelial growth factor expression and Ktrans in activated iBAT and beige tissues were in agreement with the increased vasculature and vascular perfusion kinetics. The iBAT and beige tissues were validated by measuring molecular markers. CONCLUSION: Increased Ktrans and decreased FF in iBAT and beige tissues were in agreement with the vascular perfusion kinetics facilitating the clearance of free fatty acids. The methodology can be extended for the screening of browning agents.

Differentiating brown and white adipose tissues by high-resolution diffusion NMR spectroscopy.

There are two types of fat tissues, white adipose tissue (WAT) and brown adipose tissue (BAT), which essentially perform opposite functions in whole body energy metabolism. There is a large interest in identifying novel biophysical properties of WAT and BAT by a quantitative and easy-to-run technique. In this work, we used high-resolution pulsed field gradient diffusion NMR spectroscopy to study the apparent diffusion coefficient (ADC) of fat molecules in rat BAT and WAT samples. The ADC of fat in BAT and WAT from rats fed with a chow diet was compared with that of rats fed with a high-fat diet to monitor how the diffusion properties change due to obesity-associated parameters such as lipid droplet size, fatty acid chain length, and saturation. Feeding a high-fat diet resulted in increased saturation, increased chain lengths, and reduced ADC of fat in WAT. The ADC of fat was lower in BAT relative to WAT in rats fed both chow and high-fat diets. Diffusion of fat was restricted in BAT due to the presence of small multilocular lipid droplets. Our findings indicate that in vivo diffusion might be a potential way for better delineation of BAT and WAT in both lean and obese states.

Longitudinal metabolic imaging of hepatocellular carcinoma in transgenic mouse models identifies acylcarnitine as a potential biomarker for early detection.

The cumulative effects of hepatic injury due to hepatitis B virus (HBV) infections and aflatoxin-B1 (AFB1) exposure are the major risk factors of HCC. Understanding early metabolic changes involving these risk factors in an animal model closely resembling human hepatocellular carcinoma (HCC) is critical for biomarker discovery and disease therapeutics. We have used the hepatitis B surface antigen (HBsAg) transgenic mouse model that mimics HBV carriers with and without AFB1 treatment. We investigated early metabolic changes from preneoplastic state to HCC by non-invasive longitudinal imaging in three HCC groups of mice: HBsAg + AFB1(Gp-I), AFB1 alone (Gp-II), HBsAg alone (Gp-III) and a control group (wild-type untreated; Gp-IV). For the first time, we have identified acylcarnitine signals in vivo in the liver prior to the histological manifestation of the tumors in all three groups. Acylcarnitine concentration increased with increase in tumor growth in all HCC mouse models, indicating elevated metabolic activity and increased cell turnover. This was confirmed in a pilot study using human serum from HCC patients, which revealed a higher concentration of acylcarnitine compared with normal subjects. Translational clinical studies can be designed to detect acylcarnitine in patients with high risk factors for HCC.

Multi-echo susceptibility-weighted imaging and histology of open-field blast-induced traumatic brain injury in a rat model.

Blast-induced traumatic brain injury is on the rise, predominantly as a result of the use of improvised explosive devices, resulting in undesirable neuropsychological dysfunctions, as demonstrated in both animals and humans. This study investigated the effect of open-field blast injury on the rat brain using multi-echo, susceptibility-weighted imaging (SWI). Multi-echo SWI provided phase maps with better signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), making it a sensitive technique for brain injury. Male Sprague-Dawley rats were subjected to a survivable blast of 180 kPa. The visibility of blood vessels of varying sizes improved with multi-echo SWI. Reduced signal intensity from major vessels post-blast indicates increased deoxyhaemoglobin. Relative cerebral blood flow was computed from filtered phase SWI images using inferred changes in oxygen saturation from major blood vessels. Cerebral blood flow decreased significantly at day 3 and day 5 post-blast compared with that pre-blast. This was substantiated by the upregulation of ß-amyloid precursor protein (ß-APP), a marker of ischaemia, in the neuronal perikaya of the cerebral cortex, as observed by immunofluorescence, and in the cortical tissue by western blot analysis. Our findings indicate the presence of brain ischaemia in post-blast acute phase of injury with possible recovery subsequently. Our results from cerebrovascular imaging, histology and staining provide an insight into the ischaemic state of the brain post-blast and may be useful for prognosis and outcome.

Multiple myeloma with lung plasmacytoma.

Malignant myeloma (MM) is a clonal proliferation of plasma cells with multiple osteolytic lesions. Extramedullary dissemination of multiple myeloma in lung is relatively uncommon. Hereby, we present a case of multiple myeloma with lung plasmacytoma of lung in a 45-years-old, non-smoker, female.

Development of bilateral chylothorax in a younger female secondary to tuberculosis.

Chylothorax is a rare clinical entity characterized by a milky white aspirate with increased triglyceride levels. The commonest etiology is malignancy and trauma, and bilateral chylothorax, secondary to tuberculosis, is an extremely rare cause, as observed in the present case.

Parotid tuberculosis.

Tuberculosis of the parotid gland is a rare condition. We describe a case of tuberculosis of right parotid gland in a 17-year-old male patient. Diagnosis was made by early suspicion and confirmed by demonstration of epitheloid granulomas on fine needle aspiration cytology (FNAC). Patient was successfully treated with daily regimen of four drugs (rifampicin, isoniazid, pyrazinamide, ethambutol) for first two months followed by two drugs (rifampicin and isoniazid) for last four months.

Pyrazinamide induced thrombocytopenia.

Thrombocytopenia is an uncommon but potentially life-threatening complication of certain antitubercular drugs and is characterized by rapid destruction of platelets whenever offending drug is taken by a susceptible person. We report a case of pyrazinamide-induced thrombocytopenia in a patient receiving anti tubercular drugs.

Concomittant pulmonary tuberculosis and borderline leprosy with type-II lepra reaction in single patient.

The concommitant occurrence of both tuberculosis and leprosy in a single individual are not an uncommon clinical condition but is being reported infrequently in literature. We report a case of leprosy, diagnosed previously and also diagnosed as pulmonary tuberculosis.

Comparative evaluation of dynamic contrast-enhanced perfusion with diffusion tensor imaging metrics in assessment of corticospinal tract infiltration in malignant glioma.

OBJECTIVE: To compare dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with diffusion tensor imaging (DTI) for predicting tumor infiltration in a conventional MRI normal-appearing internal capsule adjacent to the tumor in patients with glioblastoma multiforme. METHODS: Thirty patients with glioblastoma multiforme underwent a neurological examination for motor assessment, DCE MRI, and DTI. On fused DCE and DTI images, regions of interest were placed on the normal-appearing internal capsule and the corresponding region of the contralateral internal capsule. These patients were pooled into group 1 (improved after surgery, n = 9) and group 2 (did not improve after surgery, n = 21) on the basis of motor strength. The DTI and perfusion metrics were statistically analyzed to look for a predictor of motor functionality. RESULTS: Multivariate logistic regression analysis showed only cerebral blood volume to be the predictor of improvement in motor functionality after surgery (P = 0.043). CONCLUSIONS: We conclude that cerebral blood volume appears to be the predictor of motor functionality after surgery and may indirectly suggest tumor infiltration, whereas DTI helps to precisely localize the fiber tracts.

Hemorrhagic pleural effusion secondary to sarcoidosis: A brief review.

Pleural effusion is considered to be a rare manifestation of pulmonary sarcoidosis, but hemorrhagic effusion secondary to it is a very uncommon clinical presentation. This case is reported due to the rare manifestation in pulmonary sarcoidosis presenting clinically as hemorrhagic pleural effusion.

Pulmonary and nodal multiple myeloma with a pleural effusion mimicking bronchogenic carcinoma.

Multiple myeloma (MM) is a hematological malignancy characterized by the occurrence of plasma cell tumor within the bone marrow. Extramedullary plasmacytomas form a small percentage of plasma cell tumors, and although 80-90% of extramedullary lesions occur in the head and neck, pulmonary plasmacytomas are found to be a very uncommon clinical entity. Hereby, we describe a case of a patient with pulmonary plasmacytoma, who developed nodal and pulmonary MM with a pleural effusion, the radiological appearance of which mimicked bronchogenic carcinoma.

Intralobar sequestration of lung.

Intralobar pulmonary sequestration is characterized by the presence of nonfunctional parenchymal lung tissue, receiving systemic arterial blood supply. It lacks normal communication with tracheobronchial tree. Failure to diagnose and treat this condition can lead to recurrent pneumonia and fatal hemoptysis. The aim of this case report is to increase awareness about the condition and to review criteria of its definitive diagnosis and subsequent treatment.

Bilateral chylothorax in a child after mild trauma.

Chylothorax is a life-threatening form of pleural effusion with a varied aetiology. In this report, we describe the case of a child who developed bilateral chylothorax following minor trauma which responded well to conservative management.

Endobronchial metastasis of follicular thyroid carcinoma presenting as hemoptysis: a case report.

Endobronchial metastasis secondary to follicular thyroid carcinoma is extremely rare. Here, we report a case of follicular thyroid cancer in 58-year-old male who presented with hemoptysis. Computed tomography of the chest revealed multiple lung metastases. Flexible fiberoptic bronchoscopy revealed a fragile polypoid mass 5 cm distal to the vocal cords; biopsy taken from this mass revealed follicular thyroid carcinoma.