Stereogenic Harmony Fabricated Mechanoresponsive Homochiral Triphenylalanine Analogues with Synergistic Antibacterial Performances: A Potential Weapon for Dermal Wound Management.

The wound recovery phenomenon remains as one of the long challenging concerns worldwide. In search of user-friendly dressing materials, in this report, we fabricated a rational combinatorial strategy utilizing stereogenic harmony in a triphenylalanine fragment and appending it to δ-amino valeric acid at the N-terminus (hydrogelators I-VII) such that a potential scaffold could be fished out from the design. Our investigations revealed that all the hydrogelators displayed not only excellent self-healing performance as well as high mechanical strength at physiological pH but also mechanical stress-triggered gel-sol-gel transition properties. The structural and morphological investigation confirmed the presence of ß-sheet-like assemblies stabilized by intermolecular H-bonding and π-π interactions. Moreover, these scaffolds showed substantial antibacterial as well as antifungal efficacy against common wound pathogens, i.e, four Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, B. subtilis, E. fecalis), four Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, P. aerugonosa, Proteus spp.), and two fungal strains (C. albicans and A. niger). The manifestation of consistent antioxidant properties might be due to the enhancement of amphiphilicity in hydrogelators, which has led to the generation of reactive oxygen species (ROS) in a facile manner, a probable mechanism to damage the microbial membrane, the driving force behind the antimicrobial efficacy. Also, the constructs exhibited proteolytic resistance and remarkable biocompatibility toward mammalian cells. Thus, based on the above benchmarks, the homochiral hydrogelator IV was seived out from a pool of seven, and we proceeded toward its in vivo evaluation using full-thickness excisional wounds in Wister rats. The scaffolds also accentuated the re-epithelialization as well in comparison to the negative control, thereby facilitating the wound closure process in a very short span of time (10 days). Overall, our in vitro and in vivo analysis certifies hydrogelator IV as an ideal dressing material that might hold immense promise for future wound care management.

Neuroprotective effects of combined trimetazidine and progesterone on cerebral reperfusion injury.

Cerebral ischemia-reperfusion injury induces multi-dimensional damage to neuronal cells through exacerbation of critical protective mechanisms. Targeting more than one mechanism simultaneously namely, inflammatory responses and metabolic energy homeostasis could provide additional benefits to restrict or manage cerebral injury. Being proven neuroprotective agents both, progesterone (PG) and trimetazidine (TMZ) has the potential to add on the individual therapeutic outcomes. We hypothesized the simultaneous administration of PG and TMZ could complement each other to synergize, or at least enhance neuroprotection in reperfusion injury. We investigated the combination of PG and TMZ on middle cerebral artery occlusion (MCAO) induced cerebral reperfusion injury in rats. Molecular docking on targets of energy homeostasis and apoptosis assessed the initial viability of PG and TMZ for neuroprotection. Animal experimentation with MCA induced ischemia-reperfusion (I/R) injury in rats was performed on five randomized groups. Sham operated control group received vehicle (saline) while the other four I-R groups were pre-treated with vehicle (saline), PG (8 â€‹mg/kg), TMZ treated (25 â€‹mg/kg), and PG â€‹+ â€‹TMZ (8 and 25 â€‹mg/kg) for 7 days by intraperitoneal route. Neurological deficit, infarct volume, and oxidative stress were evaluated to assess the extent of injury in rats. Inflammatory reactivity and apoptotic activity were determined with alterations in myeloperoxidase (MPO) activity, blood-brain barrier (BBB) permeability, and DNA fragments. Reperfusion injury inflicted cerebral infarct, neurological deficit, and shattered BBB integrity. The combination treatment of PG and TMZ restricted cellular damage indicated by significant (p â€‹< â€‹0.05) decrease in infarct volume and improvement in free radical scavenging ability (SOD activity and GSH level). MPO activity and LPO decreased which contributed in improved BBB integrity in treated rats. We speculate that inhibition of inflammatory and optimum energy utilization would critically contribute to observed neuroprotection with combined PG and TMZ treatment. Further exploration of this neuroprotective approach for post-recovery cognitive improvement is worth investigating.

Combination therapy for cerebral ischemia: do progesterone and noscapine provide better neuroprotection than either alone in the treatment?

Ischemic stroke presents multifaceted pathological outcomes with overlapping mechanisms of cerebral injury. High mortality and disability with stroke warrant a novel multi-targeted therapeutic approach. The neuroprotection with progesterone (PG) and noscapine (NOS) on cerebral ischemia-reperfusion (I-R) injury was demonstrated individually, but the outcome of combination treatment to alleviate cerebral damage is still unexplored. Randomly divided groups of rats (n = 6) were Sham-operated, I-R, PG (8 mg/kg), NOS (10 mg/kg), and PG + NOS (8 mg/kg + 10 mg/kg). The rats were exposed to bilateral common carotid artery occlusion, except Sham-operated, to investigate the therapeutic outcome of PG and NOS alone and in combination on I-R injury. Besides the alterations in cognitive and motor abilities, we estimated infarct area, oxidative stress, blood-brain barrier (BBB) permeability, and histology after treatment. Pharmacokinetic parameters like Cmax, Tmax, half-life, and AUC0-t were estimated in biological samples to substantiate the therapeutic outcomes of the combination treatment. We report PG and NOS prevent loss of motor ability and improve spatial memory after cerebral I-R injury. Combination treatment significantly reduced inflammation and restricted infarction; it attenuated oxidative stress and BBB damage and improved grip strength. Histopathological analysis demonstrated a significant reduction in leukocyte infiltration with the most profound effect in the combination group. Simultaneous analysis of PG and NOS in plasma revealed enhanced peak drug concentration, improved AUC, and prolonged half-life; the drug levels in the brain have increased significantly for both. We conclude that PG and NOS have beneficial effects against brain damage and the co-administration further reinforced neuroprotection in the cerebral ischemia-reperfusion injury.

Renin angiotensin aldosterone system in pulmonary fibrosis: Pathogenesis to therapeutic possibilities.

Pulmonary fibrosis is a devastating lung disease with multifactorial etiology characterized by alveolar injury, fibroblast proliferation and excessive deposition of extracellular matrix proteins, which progressively results in respiratory failure and death. Accumulating evidence from experimental and clinical studies supports a central role of the renin angiotensin aldosterone system (RAAS) in the pathogenesis and progression of idiopathic pulmonary fibrosis. Angiotensin II (Ang II), a key vasoactive peptide of the RAAS mediates pro-inflammatory and pro-fibrotic effects on the lungs, adversely affecting organ function. Recent years have witnessed seminal discoveries in the field of RAAS. Identification of new enzymes, peptides and receptors has led to the development of several novel concepts. Of particular interest is the establishment of a protective axis of the RAAS comprising of Angiotensin converting enzyme 2 (ACE2), Angiotensin-(1-7) [Ang-(1-7)], and the Mas receptor (the ACE2/Ang-(1-7)/Mas axis), and the discovery of a functional role for the Angiotensin type 2 (AT2) receptor. Herein, we will review our current understanding of the role of RAAS in lung fibrogenesis, provide evidence on the anti-fibrotic actions of the newly recognized RAAS components (the ACE2/Ang-(1-7)/Mas axis and AT2 receptor), discuss potential strategies and translational efforts to convert this new knowledge into effective therapeutics for PF.

Preferential cyclooxygenase inhibition by Jasminum sambac: A possible relationship with potent anti-arthritic activity.

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Noscapine alleviates cerebral damage in ischemia-reperfusion injury in rats.

With high unmet medical needs, stroke remains an intensely focused research area. Although noscapine is a neuroprotective agent, its mechanism of action in ischemic-reperfusion (I-R) injury is yet to be ascertained. We investigated the effect of noscapine on the molecular mechanisms of cell damage using yeast, and its neuroprotection on cerebral I-R injury in rats. Yeast, both wild-type and Δtrx2 strains, was evaluated for cell growth and viability, and oxidative stress to assess the noscapine effect at 8, 10, 12, and 20 µg/ml concentrations. The neuroprotective activity of noscapine (5 and 10 mg/kg; po for 8 days) was investigated in rats using middle cerebral artery occlusion-induced I-R injury. Infarct volume, neurological deficit, oxidative stress, myeloperoxidase activity, and histological alterations were determined in I-R rats. In vitro yeast assays exhibited significant antioxidant activity and enhanced cell tolerance against oxidative stress after noscapine treatment. Similarly, noscapine pretreatment significantly reduced infarct volume and edema in the brain. The neurological deficit was decreased and oxidative stress biomarkers, superoxide dismutase activity and glutathione levels, were significantly increased while lipid peroxidation showed significant decrease in comparison to vehicle-treated I-R rats. Myeloperoxidase activity, an indicator of inflammation, was also reduced significantly in treated rats; histological changes were attenuated with noscapine. The study demonstrates the protective effect of noscapine in yeast and I-R rats by improving cell viability and attenuating neuronal damage, respectively. This protective activity of noscapine could be attributed to potent free radical scavenging and inhibition of inflammation in cerebral ischemia-reperfusion injury.

Acromioclavicular Joint Dislocation with Ipsilateral Mid Third Clavicle, Mid Shaft Humerus and Coracoid Process Fracture - A Case Report.

INTRODUCTION: The clavicle, humerus and acromioclavicular (AC) joint separately are very commonly involved in traumatic injuries around the shoulder. Acromioclavicular joint dislocation with distal clavicle fracture is a well recognized entity in clinical practice. AC joint dislocation with mid shaft clavicle fracture is uncommon and only few cases have been reported in literature. However, to the best of our knowledge, this is the first case report to describe an acromioclavicular dislocation with ipsilateral mid shaft clavicle, mid shaft humerus and coracoid process fracture. Fractures of the humerus and clavicle along with the acromioclavicular joint dislocation were fixed at the same setting. CASE REPORT: A 65-year-old male met with a high velocity road traffic accident. Plain radiographs showed displaced mid third clavicle fracture with acromioclavicular joint dislocation with mid shaft humerus fracture. Surgical fixation was planned for humerus with interlocking nail, clavicle with locking plate and acromioclavicular joint with reconstruction of coracoclavicular ligaments. Intraoperatively, coracoid process was found to have a comminuted fracture. The operative plan had to be changed on table as coracoclavicular fixation was not possible. So acromioclavicular joint fixation was done using tension band wiring and the coracoclavicular ligament was repaired using a 2-0 ethibond. The comminuted coracoid fracture was managed conservatively. K wires were removed at 6 weeks. Early mobilization was started. CONCLUSION: In acromioclavicular joint injuries, clavicle must be evaluated for any injury. Although it is more commonly associated with distal clavicle fractures, it can be associated with middle third clavicle fractures. As plain radiographs, AP view are most of the times insufficient for viewing integrity of coracoid process, either special views like Stryker notch or CT scan may help in diagnosing such concealed injuries. When associated with fractures of the humerus and clavicle, anatomical restoration of acromioclavicular joint along with anatomical reduction and a rigid fixation of associated fractures is essential. Proper rehabilitation protocol is a must for achieving promising results. In our case, we were able to achieve a stable surgical fixation of both the fractures as well as AC joint, which enabled us to start early joint mobilization and rehabilitation.

Exploring the role of curcumin containing ethanolic extract obtained from Curcuma longa (rhizomes) against retardation of wound healing process by aspirin.

AIM: The aim of the study was to assess the curcumin containing ethanolic extract (EtOH) obtained from Curcuma longa (Cl) against retardation of wound healing by aspirin. MATERIALS AND METHODS: Wound healing process was retarded by administering the dose of 150 mg/kg body weight of aspirin orally for 9 days to observe the effect of EtOH obtained from Cl using excision and incision wound model in rats. The various parameters such as % wound contraction, epithelialization period, hydroxyproline, tensile strength were observed at variant time intervals and histopathological study was also performed. RESULTS: Curcumin containing 5% and 10% ethanolic extract ointment have shown significant (P < 0.01) wound healing activity against an aspirin (administered 150 mg/kg body weight orally for 9 days) retarded wound healing process. Topical application of ointment showed significant (P < 0.01) difference as compared to the control group. Histopathological studies also showed healing of the epidermis, increased collagen, fibroblasts and blood vessels. CONCLUSION: Ethanolic extract of Cl ointment (EtOHCl) containing 10% curcumin displayed remarkable healing process against wound retardation by aspirin.