Neuroprotective Effect of Otostegia limbata Against PTZ-Induced Mice Model of Epilepsy by Attenuated Expression of p-NFκB and TNF-α.

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures. Currently available antiepileptic drugs have severe side effects and do not offer complete cure. Herbal remedies have been used for centuries to treat many neurodegenerative disorders. Otostegia limbata L. belongs to the largest and medicinally important family Lamiaceae and is distributed in hilly areas of Pakistan. This study was designed to assess the antioxidant, anti-inflammatory, and anticonvulsant potential of O. limbata. The methanolic extract showed significant antioxidant activity assessed by (1,1-diphenyl 2-picrylhydrazyl) free-radical scavenging assay, nitric oxide scavenging, and iron chelation antioxidant assays. The methanolic extract was evaluated for its anticonvulsant effect, employing the pentylenetetrazole (PTZ)-induced mice model of epilepsy. Three different doses of O. limbata (100, 200, and 300 mg/kg) were administered orally 30 min before PTZ [50 mg/kg, intraperitoneal (i.p.)] injection, while diazepam was used as a positive control. The extract at 300 mg/kg significantly decreased the duration and increased the latency of the PTZ-induced seizures. The expression of inflammatory cytokines tumor necrosis factor α (p-TNF-α) and phosphorylated transcription factor nuclear factor kappa B (p-NF-κB), in the cortex and hippocampus of the brains of treated mice were analyzed through enzyme-linked immunosorbent assay and western blot analysis. The morphological changes and number of surviving neurons were recorded through hematoxylin and eosin staining. The seizure score and survival rate of the treated group showed considerable differences as compared to the PTZ group. TNF-α and p-NF-K b expression were downregulated as compared to the PTZ group. The anticonvulsant effect may be the outcome of the antioxidant potential and high levels of phenols and flavonoids detected in the methanolic plant extract through Fourier transform infrared spectrophotometer and gas chromatography-mass spectrometry analysis.

Multiple organ dysfunction syndrome: Contemporary insights on the clinicopathological spectrum.

Multiorgan dysfunction syndrome (MODS) remains a major complication and challenge to treat patients with critical illness in different intensive care unit settings. The exact mechanism and pathophysiology of MODS is complex and remains unexplored. We reviewed the literature from January 2011 to August 2019 to analyze the underlying mechanisms, prognostic factors, MODS scoring systems, organ systems dysfunctions, and the management of MODS. We used the search engines PubMed, MEDLINE, Scopus, and Google Scholar with the keywords "multiple organ dysfunction syndrome," "intensive care units," "multiorgan failure," "MODS scoring system," and "MODS management." The initial search yielded 3550 abstracts, of which 91 articles were relevant to the scope of the present article. A better understanding of a disease course will help differentiate the signs of an intense inflammatory response from the early onset of sepsis and minimize the inappropriate use of medications. This, in turn, will promote organtargeted therapy and prevent occurrence and progression of MODS.

Screening and characterization of selected drugs having antibacterial potential.

Due to ever increasing antibiotic resistance offered by pathogenic bacterial strains and side effects of synthetic antibiotics, thereof, there is a need to explore the effective phytochemicals from natural resources. In order to help overcoming the problem of effective natural drug and the side effects posed by the use of the synthetic drugs, five different plants namely Thymus vulgaris, Lavandula angustifolia, Rosmarinus officinalis, Cymbopogon citratus and Achillea millefolium were selected to study their antibacterial potential. Antibacterial activity and minimum inhibitory concentration (MIC) checked against the selected bacterial strains. As compared to other test plants, ethanolic extract of Rosmarinus officinalis leaves showed the most promising inhibitory effect i.e: inhibition zone (18.17± 0.44mm) against Klebsiella pneumoniae and the lowest inhibition (15.5±0.29mm) against Pseudomonas aeruginosa and Escherichia coli (p<0.05). The MIC values were recorded in the range of 1 to 20mg/ml. Screening of the selected extracts for the test plants additionally indicate some unique variations. Results were further confirmed through TLC for alkaloids and terpenoids (15% sulphuric acid and Dragedroff's reagent) in ethanolic extract. Characterization of Rosmarinus officinalis of ethanolic extract was carried out using column chromatography. The appearance of orange crystals may indicate the presence of alkaloidal bioactive compounds which need to be further investigated. The tested plants may have a potential for fighting against some infectious diseases caused by selected human pathogenic bacterial strains. This knowledge may incite a gateway to effective drug search and so on.

Microchimeric fetal cells are recruited to maternal kidney following injury and activate collagen type I transcription.

Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.

The bone marrow functionally contributes to liver fibrosis.

BACKGROUND & AIMS: Bone marrow (BM) cells may transdifferentiate into or fuse with organ parenchymal cells. BM therapy shows promise in murine models of cirrhosis, and clinical trials of bone marrow stem cell therapy for organ healing are underway. However, the BM may contribute to scar-forming myofibroblasts in various organs including the liver. We have studied this axis of regeneration and scarring in murine models of cirrhosis, including an assessment of the temporal and functional contribution of the BM-derived myofibroblasts. METHODS: Female mice were lethally irradiated and received male BM transplants. Carbon tetrachloride or thioacetamide was used to induce cirrhosis. BM-derived cells were tracked through in situ hybridization for the Y chromosome. BM transplants from 2 strains of transgenic mice were used to detect intrahepatic collagen production. RESULTS: In the cirrhotic liver, the contribution of BM to parenchymal regeneration was minor (0.6%); by contrast, the BM contributed significantly to hepatic stellate cell (68%) and myofibroblast (70%) populations. These BM-derived cells were found to be active for collagen type 1 transcription in 2 independent assays and could influence the fibrotic response to organ injury. These BM-derived myofibroblasts did not occur through cell fusion between BM-derived cells and indigenous hepatic cells but, instead, originated largely from the BM's mesenchymal stem cells. CONCLUSIONS: The BM contributes functionally and significantly to liver fibrosis and is a potential therapeutic target in liver fibrosis. Clinical trials of BM cell therapy for liver regeneration should be vigilant for the possibility of enhanced organ fibrosis.