Histopathological Studies Research Articles

A lignocellulose nanofibril-poly(vinyl alcohol) hydrogel with controlled drug delivery for wound healing

Employing lignocellulosic nanofibers (LCNF) with natural, high specific mechanical performance and abundant functional groups to design a hydrogel as a drug-sustained release carrier, which conforms to the concept of green and sustainable development. Herein, we facilely extracted carboxylated lignocellulose nanofibrils (CLCNF) from bagasse via a deep eutectic solvent (DES) and mechanical defibrillation-based strategy. The CLCNF was crosslinked with poly(vinyl alcohol) (PVA) to obtain a nanocomposite hydrogel (PVA/CLCNF/B) whereupon the mechanical strength and drug release behavior were improved in the process. Consequently, the lignocellulose nanocomposite hydrogel presented a high compression modulus (3.92 MPa) and significant sustained-release effect with a release rate of 80.73 % after 336 h. The delivery behavior of the PVA/CLCNF/B composite hydrogel could be controlled by acidic pH conditions. The TH release kinetics of PVA/CLCNF/B hydrogel in different phosphate buffer saline (PBS) followed the Korsmeyer-Peppas model better, and the release of TH occurred through the Fickian diffusion mechanism. Importantly, in vivo experiments and histopathological studies showed that TH-loaded PVA/CLCNF/B hydrogel had a superior pro-healing rate. Overall, the incorporation of CLCNF into a hydrogel may have considerable potential as a drug delivery carrier for drug release and therapy. SynopsisAdding the CLCNF from bagasse into PVA dispersions obtained a hydrogel for pH-responsive drug delivery can accelerate wound healing.

Efficacy of stem cells versus microvesicles in ameliorating chronic renal injury in rats (histological and biochemical study)

Chronic exposure to heavy metals as aluminum chloride (AlCl3) could result in severe health hazards such as chronic renal injury. The present study aimed to evaluate the therapeutic potential of adipose tissue-derived stem cells (ASCs) in comparison to their microvesicles (MV) in AlCl3-induced chronic renal injury. Forty-eight adult male Wistar rats were divided into four groups: Control group, AlCl3-treated group, AlCl3/ASC-treated group, and AlCl3/MV-treated group. Biochemical studies included estimation of serum urea and creatinine levels, oxidative biomarkers assay, antioxidant biomarkers, serum cytokines (IL-1β, IL-8, IL-10, and IL-33), real time-PCR analysis of renal tissue MALT1, TNF-α, IL-6, and serum miR-150-5p expression levels. Histopathological studies included light and electron microscopes examination of renal tissue, Mallory trichrome stain for fibrosis, Periodic acid Schiff (PAS) stain for histochemical detection of carbohydrates, and immunohistochemical detection of Caspase-3 as apoptosis marker, IL-1B as a proinflammatory cytokine and CD40 as a marker of MVs. AlCl3 significantly deteriorated kidney function, enhanced renal MDA and TOS, and serum cytokines concentrations while decreased the antioxidant parameters (SOD, GSH, and TAC). Moreover, serum IL-10, TNF-α, miR-150-5p, and renal MALT1 expression values were significantly higher than other groups. Kidney sections showed marked histopathological damage in both renal cortex and medulla in addition to enhanced apoptosis and increased inflammatory cytokines immunoexpression than other groups. Both ASCs and MVs administration ameliorated the previous parameters levels with more improvement was detected in MVs-treated group. In conclusion: ASCs-derived MVs have a promising ameliorating effect on chronic kidney disease.

Repeat Femtosecond-Assisted Anterior Lamellar Keratoplasty for Recurrence of TGF B I Dystrophy in Eyes After Previous FALK.

To report the management of recurrent TGF BI dystrophy after prior femtosecond-assisted anterior lamellar keratoplasty (FALK) with repeat FALK. Clinical and histopathological study of 2 eyes of 2 patients with a recurrence of TGFBI dystrophy. Patient 1 had Reis-Buckler corneal dystrophy, and patient 2 had granular corneal dystrophy GCD type 1. Patient 1 had FALK 8 years ago, when she was 23 years old. Patient 2 had FALK 7 years ago at the age of 24 years. Slit-lamp examination showed recurrence in the subepithelial layer of the anterior lamellar graft as confluent chalky white granular deposits. Anterior segment optical coherence tomography highlighted the deposits in the subepithelial region of the anterior lamellar graft. The anterior lamellar graft with deposits was removed and replaced with another graft created using femtolaser dissection of a healthy donor. The parameters for femtosecond laser-assisted donor dissection was similar to the size and depth as the previously used donor. The best-corrected visual acuity was restored to 20/30 in patient 1 and 20/25 in patient 2. The histology of the anterior lamellar graft showed eosinophilic deposits between the epithelium and the Bowman layer in both samples. In addition, the corneal sample from patient 2 revealed Bowman layer breach at some places and few deposits at 1 edge of the lamellar graft. Repeat FALK with a healthy donor is effective in the management of recurrence of deposits. The histology of the recurrence in the anterior lamellar graft revealed eosinophilic deposits predominantly between the epithelium and Bowman layer.

Effect of dried cauliflower leaf meal (Brassica oleracea var botrytis) dietary supplementation on the growth performance, carcass and meat characteristics of rabbits.

The purpose of this study is to investigate the effect of feeding cauliflower leaf meal (CLM) on growth performance, nutrient utilization, carcass characteristics, histopathology and economics of rabbit production. A total of eighteen 45-day-old Newzeland White rabbits were randomly divided into three groups and fed with control (0%), 20% and 30% CLM in concentrate mixture and feeding trial continued for 3 months. Growth performance was recorded upto the end of the trial. On completion of the growth study, a digestibility trial was conducted to assess the digestibility of nutrients. Afterwards, all the experimental rabbits were slaughtered to evaluate the carcass and meat quality, and to examine histological changes in the viscera. The cost of production was calculated on the basis of partially replacing wheat bran with CLM. Results showed that the body weight gain, feed intake, feed conversion ratio and digestibility of nutrients were similar among the groups of rabbits. Further, dressing percentage, wholesome cut yield, chemical composition of meat, sensory evaluation, water holding capacity and shear force value were also comparable among all groups. However, total phenolic content, vitamin A and E, and polyunsaturated fatty acid were significantly (p < 0.05) higher and 2-Thiobarbituric acid reactive substance was significantly (p < 0.05) lower in 30% CLM-fed group. Histopathological study showed no pathological changes in viscera of rabbits fed with CLM. Moreover, the cost of production was significantly (p < 0.05) lower in 30% CLM-fed group of rabbits. The present work shows that the 30% CLM can be incorporated in concentrate mixture in rabbit diet without affecting growth performance or meat quality and successfully used in rabbit nutrition, which will be cheaper with enhanced keeping quality of meat.

Enhanced Antibacterial Activity of Clindamycin Using Molecularly Imprinted Polymer Nanoparticles Loaded with Polyurethane Nanofibrous Scaffolds for the Treatment of Acne Vulgaris.

Acne vulgaris, a prevalent skin condition, arises from an imbalance in skin flora, fostering bacterial overgrowth. Addressing this issue, clindamycin molecularly imprinted polymeric nanoparticles (Clin-MIP) loaded onto polyurethane nanofiber scaffolds were developed for acne treatment. Clin-MIP was synthesized via precipitation polymerization using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and azoisobutyronitrile (AIBN) as functional monomers, crosslinkers, and free-radical initiators, respectively. MIP characterization utilized Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) before being incorporated into polyurethane nanofibers through electrospinning. Further analysis involved FTIR, scanning electron microscopy (SEM), in vitro release studies, and an ex vivo study. Clin-MIP showed strong antibacterial activity against S. aureus, with inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.39 and 6.25 μg/mL, respectively. It significantly dropped the bacterial count from 1 × 108 to 39 × 101 CFU/mL in vivo and has bactericidal activity within 180 min of incubation in vitro. The pharmacodynamic and histopathology studies revealed a significant decrease in infected animal skin inflammation, epidermal hypertrophy, and congestion upon treatment with Clin-MIP polyurethane nanofiber and reduced pro-inflammatory cytokines (NLRP3, TNF-α, IL-1β, and IL-6) conducive to acne healing. Consequently, the recently created Clin-MIP polyurethane nanofibrous scaffold. This innovative approach offers insight into creating materials with several uses for treating infectious wounds caused by acne.

Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy

Myositis with anti-Ku-autoantibodies is a rare inflammatory myopathy associated with various connective tissue diseases. Histopathological studies have identified inflammatory and necrotizing aspects, but a precise morphological analysis and pathomechanistic disease model are lacking. We therefore aimed to carry out an in-depth morpho-molecular analysis to uncover possible pathomechanisms. Muscle biopsy specimens from 26 patients with anti-Ku-antibodies and unequivocal myositis were analyzed by immunohistochemistry, immunofluorescence, transcriptomics, and proteomics and compared to biopsy specimens of non-disease controls, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Clinical findings and laboratory parameters were evaluated retrospectively and correlated with morphological and molecular features. Patients were mainly female (92%) with a median age of 56.5 years. Isolated myositis and overlap with systemic sclerosis were reported in 31%, respectively. Isolated myositis presented with higher creatine kinase levels and cardiac involvement (83%), whereas systemic sclerosis-overlap patients often had interstitial lung disease (57%). Histopathology showed a wide spectrum from mild to pronounced myositis with diffuse sarcolemmal MHC-class I (100%) and -II (69%) immunoreactivity, myofiber necrosis (88%), endomysial inflammation (85%), thickened capillaries (84%), and vacuoles (60%). Conspicuous sarcoplasmic protein aggregates were p62, BAG3, myotilin, or immunoproteasomal beta5i-positive. Proteomic and transcriptomic analysis identified prominent up-regulation of autophagy, proteasome, and hnRNP-related cell stress. To conclude, Ku + myositis is morphologically characterized by myofiber necrosis, MHC-class I and II positivity, variable endomysial inflammation, and distinct protein aggregation varying from IBM and IMNM, and it can be placed in the spectrum of scleromyositis and overlap myositis. It features characteristic sarcoplasmic protein aggregation on an acquired basis being functionally associated with altered chaperone, proteasome, and autophagy function indicating that Ku + myositis exhibit aspects of an acquired inflammatory protein-aggregate myopathy.

Aortic aneurysms in patients with atherosclerotic coronary artery disease in the southwestern region of Romania - clinical and histopathological study.

An aneurysm is defined as a dilation of the arterial wall with a diameter exceeding 1.5 times the normal diameter of the vessel concerned. Aortic aneurysms (AAs) can develop at any level but are mostly found at the abdominal and infrarenal levels and extend to the iliac arteries. AAs are usually asymptomatic and are most often discovered incidentally during various imaging investigations for other conditions. Rupture of an AA is usually dramatic, being one of the causes of sudden cardiac death. Surgical treatment and, more recently, endovascular treatment are the only effective methods of AA repair. In this study, we screened for the diagnosis of AAs in patients with stable exertional angina who had indications for coronary angiography. The study was carried out in the period 2021-2023 in the Institute of Cardiovascular Diseases Timişoara, Romania. Of the 2458 patients with exertional angina who required coronary angiography, a number of 1844 (75%) patients had at least one stenotic atheromatous plaque, and of these 312 patients had AAs, of which 173 at the level of the abdominal aorta.

Primary alveolar soft part sarcoma of the ilium: A case report and literature review

Introduction: The primary alveolar soft part sarcoma (ASPS) of bone is extremely rare, and the number of published reporting cases is limited. Case Report: We present a 30-year-old woman with primary ASPS of ilium. Computed tomography and magnetic resonance imaging revealed a destructive and moth-eaten appearance in the ilium with a soft tissue mass. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed high uptakes of FDG in the left ilium. ASPSCR1-TFE3 gene fusion was detected by reverse transcriptase polymerase chain reaction (RT-PCR). Wide resection was performed. One year after the surgery, a local recurrence developed. However, there has been no evidence of disease in the last eight years after the second surgery. Conclusion: 18F-fluorodeoxyglucose positron emission tomography-computed tomography and RT-PCR besides routine radiological and histopathological studies helped achieve the accurate diagnosis and provide appropriate treatment in the present case.

Unusual case report: Nodule of heterotopic pancreatic tissue found attached to the gall bladder wall

The occurrence of heterotopic pancreas, an uncommon developmental abnormality, is frequently detected as an incidental finding. In a histopathological study, a 35-year-old woman with cholecystitis was unexpectedly found to have a 5 mm diameter heterotopic pancreatic tissue attached to the gallbladder wall, presenting as a nodule. Following the surgical removal of the gallbladder (cholecystectomy), the patient experienced a smooth recovery. Identifying this condition may offer valuable insights into its clinical significance.

Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats

BackgroundEpisodes of recurrent or severe hypoglycemia can occur in patients with diabetes mellitus, insulinoma, neonatal hypoglycemia, and medication errors. However, little is known about the short-term and long-term effects of repeated episodes of acute severe hypoglycemia on the brain, particularly in relation to hippocampal damage and cognitive dysfunction.MethodsThirty-six wistar rats were randomly assigned to either the experimental or control group. The rats were exposed to severe hypoglycemia, and assessments were conducted to evaluate oxidative stress in brain tissue, cognitive function using the Morris water maze test, as well as histopathology and immunohistochemistry studies. The clinical and histopathological evaluations were conducted in the short-term and long-term.ResultsThe mortality rate attributed to hypoglycemia was 34%, occurring either during hypoglycemia or within 24 h after induction. Out of the 14 rats monitored for 7 to 90 days following severe/recurrent hypoglycemia, all exhibited clinical symptoms, which mostly resolved within three days after the last hypoglycemic episode, except for three rats. Despite the decrease in catalase activity in the brain, the total antioxidant capacity following severe insulin-induced hypoglycemia increased. The histopathology findings revealed that the severity of the hippocampal damage was higher compared to the brain cortex 90 days after hypoglycemia. Memory impairments with neuron loss particularly pronounced in the dentate gyrus region of the hippocampus were observed in the rats with severe hypoglycemia. Additionally, there was an increase in reactive astrocytes indicated by GFAP immunoreactivity in the brain cortex and hippocampus.ConclusionRecurrent episodes of severe hypoglycemia can lead to high mortality rates, memory impairments, and severe histopathological changes in the brain. While many histopathological and clinical changes improved after three months, it seems that the vulnerability of the hippocampus and the development of sustained changes in the hippocampus were greater and more severe compared to the brain cortex following severe and recurrent hypoglycemia. Furthermore, it does not appear that oxidative stress plays a central role in neuronal damage following severe insulin-induced hypoglycemia. Further research is necessary to assess the consequences of repeated hypoglycemic episodes on sustained damage across various brain regions.

Potential anxiolytic therapeutics from Hybanthus enneaspermus (L.) F. Muell. - mitigate anxiety by plausibly modulating the GABAA-Cl- channel

Anxiety is a commonly prevailing psychological disorder that requires effective treatment, wherein phytopharmaceuticals and nutraceuticals could offer a desirable therapeutic profile. Hybanthus enneaspermus (L.) F. Muell. is a powerful medicinal herb, reportedly effective against several ailments, including psychological disorders. The current research envisaged evaluating the anxiolytic potential of the ethanolic extract of Hybanthus enneaspermus (EEHE) and its toluene insoluble biofraction (ITHE) employing experimental and computational approaches. Elevated Plus Maze, Light and Dark Transition, Mirror Chamber, Hole board and Open field tests were used as screening models to assess the antianxiety potential of 100, 200 and 400 mg/kg body weight of EEHE and ITHE in rats subjected to social isolation, using Diazepam as standard. The brains of rats exhibiting significant anxiolytic activity were dissected for histopathological and biochemical studies. Antioxidant enzymes like catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase; and neurotransmitters viz. monoamines (serotonin, noradrenaline, dopamine), Gamma-aminobutyric acid (GABA), and glutamate were quantified in the different regions of rats’ brain (cortex, hippocampus, pons, medulla oblongata, cerebellum). Chromatographic techniques were used to isolate phytoconstituents from the fraction exhibiting significant activity that were characterized by spectroscopic methods and subjected to in silico molecular docking. ITHE at 400 mg/kg body weight significantly mitigated anxiety in all the screening models (p < 0.05), reduced the inflammatory vacuoles and necrosis (p < 0.05) and potentiated the antioxidant enzymes (p < 0.05). It enhanced the monoamines and GABA levels while attenuating glutamate levels (p < 0.01) in the brain. Three significant flavonoids viz. Quercitrin, Rutin and Hesperidin were isolated from ITHE. In silico docking studies of these flavonoids revealed that the compounds exhibited substantial binding to the GABAA receptor. ITHE displayed a promising pharmacological profile in combating anxiety and modulating oxidative stress, attributing its therapeutic virtues to the flavonoids present.

Evaluation of the anti-inflammatory, antinociceptive, and antipyretic potential of ethanolic extract of Aristida depressa Retz through in vitro, in vivo, and in silico models.

Uncontrolled inflammation is a crucial factor in the development of many diseases. Anti-inflammatory molecules based on natural sources are being actively studied, among which Aristida depressa Retz (Ar.dp) has been traditionally used as a paste to heal inflammation. The present study aimed to evaluate the anti-inflammatory, analgesic, and antipyretic potential of an ethanolic extract of A. depressa through a battery of in vivo and in vitro models. The ethanolic extract of A. depressa was prepared by maceration and chemically characterized using high-performance liquid chromatography, which revealed the presence of quercetin, vanillic acid, chlorogenic acid, p-coumaric acid, m-coumaric acid, ferulic acid, cinnamic acid, and sinapic acid; its antioxidant capacity was then screened with the DPPH in vitro assay, which indicated moderate scavenging capacity. A protein denaturation assay was next performed to evaluate the in vitro anti-inflammatory potential of Ar.dp, which showed significant inhibition (44.44%) compared to the standard drug (diclofenac sodium), with 89.19% inhibition at a concentration of 1mg/mL. The in vivo safety profile of Ar.dp was evaluated in accordance with the OECD-425 acute toxicity guidelines and found to be safe up to 5g/kg. The in vivo anti-inflammatory potentials of Ar.dp were evaluated at three different doses (125, 250, and 500mg/kg) in acute (carrageenan-induced edema: 84.60%, histamine-induced paw edema: 84%), sub-chronic (cotton-pellet-induced granuloma: 57.54%), and chronic (complete-Freund's-adjuvant-induced arthritis: 82.2%) models. Our results showed that Ar.dp had significant (p < 0.05) anti-inflammatory effects over diclofenac sodium in the acute and chronic models. Histopathology studies indicated reduced infiltration of paw tissues with inflammatory cells in Ar.dp-treated animals. Similarly, Ar.dp showed significant (p < 0.05) analgesic (yeast-induced-pyrexia model: 23.53%) and antipyretic (acetic-acid-induced writhing model: 51%) effects in a time-dependent manner. In silico studies on the interactions of COX-1 and COX-2 with the eight ligands mentioned earlier confirmed the inhibition of enzymes responsible for inflammation and fever. Based on the findings of the present study, it is concluded that Ar.dp has anti-inflammatory, analgesic, and antipyretic properties that are likely linked to its pharmacologically active phenolic bioactive molecules.

Hepatoprotective Activity of Patra Swarasa of Guduchi (Tinospora Cordifolia) Against- Paracetamol Induced

Guduchi (Tinospora cordifolia (Willd.) Miers], Menispermaceae family, it is important medicinal plant is widely distributed through India. It is categorized as "Rasayana" and the whole plant is used medicinally. The aim of the present study is to evaluate the protective effect of Guduchi patra swaras against paracetamol induced liver damage in Wister albino rats. Material &amp; Methods: Wistar Albino rats (140-250g) will be divided into 6 group and each group 6 rats, into control group, paracetamol control, standard group, test group. The test drug Guduchi patra swarasa was administered orally for 10 consecutive days and two dose of the toxicant (paracetamol) were administered orally to each group, on two alternate days i.e., 7th and 9th day, 1hr after test drug administration. After 48 hours of toxicant paracetamol, and standard group. The blood was collected in EDTA tube and sent for biochemistry laboratory for biochemical investigations. Result: The analysis of serum biochemical parameters shows that administration of paracetamol leads to significant change in majority of the parameters. The overall activity profile indicated reversal of important parameters like SGOT, SGPT, total bilirubin, total protein, blood sugar level, serum globulin, serum albumin, serum total cholesterol and serum triglycerides. All three test groups of Guduchi patra Swarasa administered are found to be effective heapto-protective especially based on histo-pathological study. Among the three groups, the double dose group and therapeutic group has shown good results in comparison with the other two groups. Conclusion: In the present study, the overall activity profile of Guduchi patra Swarasa administered are found to be effective hepatoprotective among the three groups therapeutic double dose shows good results in comparison with the other group.

The hydro-ethanolic extract of Scoparia dulcis Linn inhibits allergic airway inflammatory responses in murine asthma models

BackgroundInflammatory responses, including airway inflammation, hyper-responsiveness, mucus hyper-secretion, prostaglandins and Th2 cytokines infiltration in the airway submucosa, frequently occur in allergic respiratory disorders. This study sought to investigate the effects of the hydro-ethanolic extract of Scoparia dulcis (SDE) on allergic airway inflammation, airway hyper-responsiveness, goblet cell hyperplasia, mucus hypersecretion, Th2 cytokines and prostaglandin (PG)-D2 using murine asthma models. MethodsAllergic asthma was induced in healthy guinea-pigs, and mice, by exposing them to ovalbumin (OVA) sensitization and challenge, and treatment with either 2 ml/kg normal saline, 10 mg/kg salbutamol, 10 mg/kg prednisolone, 50, 100, or 250 mg/kg of SDE per os. The percentage protection against pre-convulsive dyspnoea after methacholine challenge in OVA-induced asthmatic guinea-pigs was determined for each treatment regime, and histopathological examinations thereafter conducted on the excised lungs. Periodic acid-Schiff staining was also performed to identify goblet cell hyperplasia and mucus hypersecretion in these lung tissues. Lung tissue homogenates and serum from OVA-induced asthmatic mice were also assayed for PGD2, interleukins (IL)-5 and -13 levels using monoclonal antibody-based mouse ELISA kits. ResultsSDE treatments prolonged the time taken for pre-convulsive dyspnoea to occur after methacholine challenge in OVA-induced asthmatic guinea-pigs; indicative of a positive activity against airway hyper-responsiveness. Histopathological studies also showed that SDE significantly inhibited (p ≤ 0.05) pulmonary infiltration of leukocytes, inflammatory cell accumulation, airway smooth muscle thickening and goblet cell hyperplasia. Serum and lung tissue concentrations of PGD2, IL-5 and IL-13, significantly elevated (p ≤ 0.001) following allergic asthma induction in mice, were significantly reduced (p ≤ 0.01) back to within normal levels after SDE treatments. ConclusionThe plant extract exhibited anti-asthmatic and anti-inflammatory properties, as it reduced the severity of allergic inflammation and hyper-reactivity, as well as PGD2 and Th2 cytokines infiltration in the airway; and these effects could be exploited for future management of asthma.

Fangchinoline protects hepatic ischemia/reperfusion liver injury in rats through anti-oxidative stress and anti-inflammation properties: an in silico study.

Liver ischemia-reperfusion (I/R) injury is a common cause of organ failure, developed by a sudden block in the blood and oxygen supply and subsequent restoration. I/R damage is responsible for acute and chronic rejection after organ transplantation, accounting for 10% of early graft failure. The study investigated the therapeutic properties of fangchinoline in liver injury-induced rats. The rats were divided into three groups: Sham, I/R without pretreatment, and I/R+10mg/kg fangchinoline pretreatment. Blood and liver samples were collected for assays, and an in silico docking analysis was conducted to determine fangchinoline's inhibitory effect. The pretreatment with 10mg/kg of fangchinoline effectively reduced hepatic marker enzymes such as AST, LDH, and ALT in the serum of rats with liver I/R damage. Fangchinoline treatment significantly reduced interleukin-8 (IL-8), IL-6, and tumor necrosis factor-α (TNF-α) in I/R-induced rats, boosting antioxidants and decreasing MDA. Histopathological studies showed liver injury protection, and fangchinoline inhibited TNF-α and IL-6 with improved binding affinity. Fangchinoline has hepatoprotective properties by reducing inflammation in rats with liver I/R damage, as demonstrated in the current study. Hence, it can be an effective salutary agent in preventing liver damage caused by I/R.

Disseminated Tuberculosis with Testes Involvement: An Intriguing Case Report

Background: Disseminated tuberculosis (TB) is the presence of two or more noncontiguous sites resulting from hematogenous dissemination of Mycobacterium tuberculosis. We report a case of disseminated TB with testicular involvement. Case: A 21-year-old male patient presented to the outpatient department with bilateral testicular enlargement and tenderness for last six months. It was suspected to be a case of epididymo-orchitis and empirical antimicrobial therapy was initiated. However, ultrasonography findings were inconsistent with epididymo-orchitis. Two weeks later the patient again presented with increased nodularity in the right testes. Non-seminomatous germ cell tumor was suspected. However, tumor markers came back normal. Magnetic resonance imaging revealed enlarged lymph nodes in the right inguinal and retroperitoneal region raising a suspicion of testicular lymphoma. Positron emission tomography with computed tomography showed multiple lymphadenopathies. Histopathology of the left axillary lymph node finally confirmed the diagnosis to be tuberculosis. No drug resistance were found and the patient responded well to anti-tubercular drugs. Conclusion: Diagnosing disseminated TB is difficult as it mimics conditions, such as infarction, cancer, torsion, etc. Attention to small details is necessary. We faced a similar situation in our patient. The patient went through a myriad of tests before finally being diagnosed with TB. Histopathological study was able to get it whereas cytology could not. Similar and totally opposite cases were found in the literature. This highlights the difficulty and importance of these type of cases.

Mitochondria mediated inhibitory effect of Nyctanthes arbor-tristis (L.) flower extract against breast adenocarcinoma and T-cell lymphoma: An in vitro and in vivo study

Ethnopharmacological relevanceThe flowers of Nyctanthes arbor-tristis (L.) heals mouth ulcers. Its tinctures promote gastric secretions, and improve lung expectoration when taken orally. It has traditionally been used to treats scabies and other skin problems. The leaves of NAT(L.) plant are used in Ayurvedic medicine to treat sciatica, chronic fever, rheumatism, internal worm infections, and as a laxative, diaphoretic, and diuretic. The bark used in treatment of snakebite and bronchitis. In addition to traditional uses, pharmacologically this plant has potent antimalarial, antiarthritic, anticancer and antidiabetic activity. However, the mechanistic antiproliferative potentials of NAT(L.) flower as anticancer therapeutics has not yet been explored. Aim of the studyThe current study is based on a broad range of scientific literature that highlights the nutritional and therapeutic benefits of NAT (L.). Present investigation was carried out to determine the therapeutic efficacy of NAT (L.) against breast adenocarcinoma cells and T-cell lymphoma. Materials and methodsThe ethyl-acetate extract of NAT(L.) was tested against breast cancer cells to assess the anticancer potential. To evaluate apoptosis, intracellular ROS levels and mitochondrial dynamics, fluorescence microscopy and flow cytometry were employed. Additionally, cell cycle analysis and western blotting were also performed. Furthermore, in vivo antitumor efficacy of flower extracts was investigated in T-cell lymphoma-bearing BALB/c mice model. ResultsOur present study revealed that NAT (L.) exert anticancer activity against breast cancer cells effectively at IC50 320 μg/ml while having less impact on normal cells with IC50 more than 480 μg/ml. Fluorescence imaging showed that NAT (L.) treatment elicits a concentration-dependent rise in the occurrence of apoptotic cell deaths with altered mitochondrial dynamics and was subsequently confirmed by flow cytometry. Further, flow cytometric analysis delineates ethyl acetate flower extract exposure promotes arrest of cells in S phase of the cell cycle. The differential expression of apoptotic proteins such as Bax, Bcl-2, cleaved PARP-1, cleaved caspase 3, Cytochrome-c, p53 and VEGF A were influenced by NAT (L.) treatment. The in vivo antitumor activity study delineates that NAT(L.) therapy significantly increased the life span of T-cell lymphoma bearing mice while reducing tumor load and belly size growth pattern without causing significant other distinct side effects as evident by histopathological studies. ConclusionOur current findings unveil that NAT(L.) ethyl acetate flower extract potentially induces mitochondrial pathway of apoptosis, promote cell cycle arrest, reduces tumor load of mice, enhances survivability and could be a promising agent against the triple negative breast cancer and lymphoma.

Silver Nanoparticles Loaded With Oleuropein Alleviates LPS-Induced Acute Lung Injury by Modulating the TLR4/P2X7 Receptor-Mediated Inflammation and Apoptosis in Rats.

Toll-like receptor 4 (TLR-4) ligands were initially shown to be the source of lipopolysaccharide (LPS), a gram-negative bacterium's cell wall immunostimulatory component. Oxidative stress, apoptosis, and inflammation are all potential effects of LPS treatment on the lungs. By triggering oxidative stress and inflammation, these negative effects could be avoided. Robust flavonoid oleuropein (OLE) exhibits anti-inflammatory, antiproliferative, and antioxidative properties. A nanodelivery system could improve its low bioavailability, making it more effective and useful in treating chronic human ailments. This study evaluates the effects of AgNP-loaded OLE on LPS-induced lung injury in rats in terms of TLR4/P2X7 receptor-mediated inflammation and apoptosis. Forty-eight male albino rats were randomly divided into eight groups. Drugs were administered to the groups in the doses specified as follows: Control, LPS (8 mg/kg ip), OLE (50 mg/kg) AgNPs (100 mg/kg), OLE + AgNPs (50 mg/kg), LPS + OLE (oleuropein 50 mg/kg ig + LPS 8 mg/kg ip), LPS + AgNPs (AgNPs 100 mg/kg ig + LPS 8 mg/kg ip), and LPS + OLE + AgNPs (OLE + AgNPs 50 mg/kg + LPS 8 mg/kg ip). After the applications, the rats were decapitated under appropriate conditions, and lung tissues were obtained. Oxidative stress (SOD, MDA, and GSH), and inflammation (IL-6, IL-1β, TNF-α, Nrf2, P2X7R, AKT, and TLR4) parameters were evaluated in the obtained lung tissues. Additionally, histopathology studies were performed on lung tissue samples. The data obtained were evaluated by comparison between groups. Both OLE and OLE + AgNPs showed potential in reducing oxidative stress, inflammation, and apoptosis (p < 0.05). These findings were supported by histopathological analysis, which revealed that tissue damage was reduced in OLE and OLE + AgNPs-treated groups. According to the results, LPS-induced lung injury can be reduced by using nanotechnology and producing OLE + AgNP.

Synthesis, COX-2 inhibition, anti-inflammatory activity, molecular docking, and histopathological studies of new pyridazine derivatives

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC50 = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1β. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs.

Effect of physical activity on the course of inflammatory bowel disease

The inflammatory bowel disease (IBD) group includes ulcerative colitis (UC), Crohn's disease (CD) and microscopic enteritis. In UC, the lesions involve only the large intestine and do not cross the mucosa, while CD can involve any part of the gastrointestinal tract, from the mouth to the anus. Inflammatory bowel disease usually occurs between the ages of 20-30, with another peak incidence in the seventh decade of life. The etiology of inflammatory bowel disease is not fully understood. Diagnosis is made on the basis of clinical evaluation, endoscopic examination with histopathological evaluation and imaging studies. Treatment involves the introduction of an appropriate diet, and pharmacological, biological and surgical treatments are used. The prognosis is inauspicious, with inflammatory lesions often recurring, even after years of remission of the disease. The purpose of this paper is to describe in detail the two most common diseases in the inflammatory bowel disease group, highlighting the differences and similarities between them at the level of lesion localization, symptoms, diagnosis and treatment. Patients with inflammatory bowel disease, due to the accompanying symptoms that make daily activities difficult, are less active than healthy people. There is ample evidence of the beneficial effects of physical activity on quality and length of life. It is recommended to conduct moderate intensity of both endurance and resistance exercises.