Transport of synaptic vesicles is modulated by vesicular reversals and stationary cargo clusters.

Stationary clusters of vesicles are a prominent feature of axonal transport, but little is known about their physiological and functional relevance to axonal transport. Here, we investigated the role of vesicle motility characteristics in modulating the formation and lifetimes of such stationary clusters, and their effect on cargo flow. We developed a simulation model describing key features of axonal cargo transport, benchmarking the model against experiments in the posterior lateral mechanosensory neurons of Caenorhabditis elegans. Our simulations included multiple microtubule tracks and varied cargo motion states, and account for dynamic cargo-cargo interactions. Our model also incorporates static obstacles to vesicle transport in the form of microtubule ends, stalled vesicles and stationary mitochondria. We demonstrate, both in simulations and in an experimental system, that a reduction in reversal rates is associated with a higher proportion of long-lived stationary vesicle clusters and reduced net anterograde transport. Our simulations support the view that stationary clusters function as dynamic reservoirs of cargo vesicles, and reversals aid cargo in navigating obstacles and regulate cargo transport by modulating the proportion of stationary vesicle clusters along the neuronal process.

Morus Alba Fruit Extract and its Fractions Ameliorate Streptozotocin Induced Cognitive Deficit in Mice via Modulating Oxidative and Cholinergic Systems.

Increased oxidative stress and acetylcholinesterase (AChE) activity are key pathological characters contributing to the memory disorders. Thus, drugs targeting both oxidative stress and AChE are being explored for the management of cognitive dysfunction. Morus alba fruits (commonly consumed for its high nutritious value) are known to have antioxidant and AChE inhibitory effects. However, the role of Morus alba fruits in the management of memory disorders has not reported yet. This investigation was conducted to assess the antioxidant and AChE inhibitory potential of Morus alba fruit extracts in-vitro and to identify the components responsible for such effects. Further, the obtained bioactive component was studied for possible memory improvement effects against streptozotocin (STZ) induced dementia. To isolate the bioactive component in-vitro DPPH and AChE assays guided fractionation was performed. Memory functions in mice were determined using Morris Water Maze test while brain biochemical parameters were measured to understand the mechanism of action. In-vitro assays revealed strong AChE and DPPH inhibitory potential of methanol extract (ME), therefore, it was further fractionated. Among various fractions obtained, ethyl-acetate fraction (EAF) was found to possess marked AChE and DPPH inhibitory activities. On subsequent fractionation of EAF, bioactivity of obtained sub-fractions was found to be inferior to EAF. Further, both ME and EAF improved STZ (intracerebroventricular) induced cognitive dysfunction in animals by restoring endogenous antioxidant status (superoxide dismutase and reduced glutathione) and reducing thiobarbituric acid reactive species and nitric oxide levels along with brain AChE and myeloperoxidase activity. TLC densitometric studies showed appreciable levels of phenolic acids and quercetin in both EAF and ME. It can be concluded that Morus alba fruit extract has the ability to modulate cholinergic and oxidative system due to presence of phenolic and flavonoid compounds and hence, could aid in the management of memory disorders.

Pharmacological insights and role of bufalin (bufadienolides) in inflammation modulation: a narrative review.

Bufadienolides, specifically bufalin, have garnered attention for their potential therapeutic application in modulating inflammatory pathways. Bufalin is derived from toad venom and exhibits promising anti-inflammatory properties. Its anti-inflammatory effects have been demonstrated by influencing crucial signaling pathways like NF-B, MAPK, and JAK-STAT, resulting in the inhibition of pro-inflammatory substances like cytokines, chemokines, and adhesion molecules. Bufalin blocks inflammasome activation and reduces oxidative stress, hence increasing its anti-inflammatory properties. Bufalin has shown effectiveness in reducing inflammation-related diseases such as cancer, cardiovascular problems, and autoimmune ailments in preclinical investigations. Furthermore, producing new approaches of medication delivery and combining therapies with bufalin shows potential for improving its effectiveness and reducing adverse effects. This review explores the pharmacological effects and mechanistic approaches of bufalin as an anti-inflammatory agent, which further highlights its potential for therapy and offers the basis for further study on its therapeutic application in inflammation-related disorders.

Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment.

Mounting evidence shows that dietary intake of fruits with polyphenols is beneficial to improve impaired memory functions. This study explored the preventive as well as therapeutic effects of diet enriched with Morus alba fruits extract (DEMA) in streptozotocin (STZ) induced mouse model of memory impairment. The study consisted of two facets: one aspect consisted of pretreatment of animals with DEMA for two weeks followed by STZ (i.c.v) intervention and the second phase involved induction of dementia with STZ (i.c.v) followed by treatment with DEMA for 14 days. Cognitive functions of animals were measured by Morris Water Maze test and to delineate the associated mechanism of action, brain biochemical estimations (acetyl-cholinesterase activity, myeloperoxidase activity, thiobarbituric acid reactive species, superoxide dismutase activity, reduced glutathione and nitrite/nitrate) and histopathological studies (haematoxylin and eosin staining) were performed. Pre- and post- treatment with DEMA significantly prevented and attenuated, respectively, the detrimental effects of STZ on mice brain. The results demonstrated that dietary modification, by incorporation of M. alba fruits, reduces the incidence and aids in treatment of memory disorder in mice by reducing central cholinergic activity, decreasing oxidative stress and preventing neurodegeneration.

One-Pot Crystallization of 2D and 3D Cobalt-Based Metal-Organic Frameworks and Their High-Performance Electrocatalytic Oxygen Evolution.

Developing highly competent and low-cost earth-plentiful metal-based oxygen evolution reaction (OER) electrocatalysts is critical for future electrochemical conversion technologies and renewable energy systems. Herein, two cobalt-based metal-organic frameworks (Co-MOFs), [Co6(btc)2(DMF)6(HCOO)6] (2D, MOF 1) and [Co3(CHOO)9{DMA}3] (3D, MOF 2), where btc = 1,3,5-benzenetricarboxylic acid, DMF = N,N-dimethylformamide, and DMA = dimethylamine, have been crystallized under hydrothermal conditions, from a single reaction. MOF 1 shows an extraordinary OER performance with 175 mV overpotential to attain 10 mA cm-2 current density with a low Tafel slope value of 80 mV dec-1, whereas MOF 2 achieves 10 mA cm-2 current density at 389 mV overpotential. Two different architecture-based MOFs have been synthesized from a single solution for the very first time. Also, the OER activity of MOF 1 overpowers the commercially used RuO2 and surpasses most of the reported OER electrocatalysts. Post OER characterization of MOF 1 revealed the in situ formation of Co(OH)2 and CoOOH, acting as active sites for the OER process.

Cargo crowding at actin-rich regions along axons causes local traffic jams.

Steady axonal cargo flow is central to the functioning of healthy neurons. However, a substantial fraction of cargo in axons remains stationary up to several minutes. We examine the transport of precursors of synaptic vesicles (pre-SVs), endosomes and mitochondria in Caenorhabditis elegans touch receptor neurons, showing that stationary cargo are predominantly present at actin-rich regions along the neuronal process. Stationary vesicles at actin-rich regions increase the propensity of moving vesicles to stall at the same location, resulting in traffic jams arising from physical crowding. Such local traffic jams at actin-rich regions are likely to be a general feature of axonal transport since they also occur in Drosophila neurons. Repeated touch stimulation of C. elegans reduces the density of stationary pre-SVs, indicating that these traffic jams can act as both sources and sinks of vesicles. This suggests that vesicles trapped in actin-rich regions are functional reservoirs that may contribute to maintaining robust cargo flow in the neuron. A video abstract of this article can be found at: Video S1; Video S2.

Outcome of pulmonary rehabilitation in patients after acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary rehabilitation (PR) is an evidence-based intervention in patients with chronic obstructive pulmonary disease (COPD) which improves the exercise capacity and quality of life (QoL). METHODS: We studied 60 patients after an episode of acute exacerbation of COPD (AECOPD). They were randomised to receive conventional treatment without pulmonary rehabilitation (CTWPR) (n=30) or, standard treatment plus a 12-week post-exacerbation pulmonary rehabilitation (PEPR) programme in addition. Assessment of exercise capacity by six minute walk test (6MWT) and QoL measured by St George's Respiratory Questionnaire (SGRQ) were carried out initially and at the end of three months. RESULTS: The baseline characteristics of both the groups were found to be similar. There was a statistically significant increase in the six minute walk distance (6MWD) (increase by 37.9 meters, p< 0.001) and a significant decline in the total SGRQ score (by 3.8 units p< 0.001) in the PEPR group compared to CTWPR group. CONCLUSION: Early pulmonary rehabilitation in patients with an AECOPD has significant benefits on the QoL and exercise capacity.

Comparison of nebulized ropivacaine (0.75%) with nebulized dexmedetomidine on the hemodynamic response on intubation in patients undergoing surgery under general anesthesia: A comparative randomized double-blind placebo-controlled study.

Background: Laryngoscopy and tracheal intubation lead to sympathetic stimulation resulting in hemodynamic fluctuations. We compared local anesthetic ropivacaine 0.75% with alpha agonist dexmedetomidine through ultrasonic nebulization for direct local action of the drug in the airway. Methods: In our randomized study, 180 patients were prospectively assigned to three groups of 60 each: group R (0.75%), group D (1 microgram/kg), and group C (control). The primary objective was to determine whether nebulized ropivacaine or nebulized dexmedetomidine can cause a reduction in stress response to laryngoscopy and intubation. The secondary objectives were to compare the hemodynamic parameters at extubation, cough response at extubation, and postoperative sore throat. Results: A total of 165 patients were analyzed. Demographically, all the groups were similar. Group R and group D were found to significantly attenuate the heart rate (HR) at intubation and extubation when compared to group C (P < 0.05). A significant reduction in mean arterial pressure (MAP) was seen (P < 0.05; group D: 90 ± 18.4 mmHg, group C: 99.5 ± 15.9 mmHg, group R: 92.4 ± 16.1 mmHg). There was a significant reduction in cough response in both groups in comparison with group C at 0 minutes (P value; group C vs group D: <.0001; group C vs group R:.01) and 5 minutes (P value; group C vs group D: <.0001; group C vs group R: <.0001). Conclusion: Preinduction topical use of ropivacaine or dexmedetomidine, through the nebulization route, effectively attenuated the pressor responses when compared to placebo.

5,7-dihydroxy-3',4',5'-trimethoxyflavone mitigates lead induced neurotoxicity in rats via its chelating, antioxidant, anti-inflammatory and monoaminergic properties.

Chronic exposure to lead (Pb) induces neurodegenerative changes in animals and humans. Drugs with strong antioxidant properties are effective against Pb-mediated neurotoxicity. In a prior study, we identified 5,7-dihydroxy-3',4',5'-trimethoxyflavone (TMF) from Ocimum basilicum L. leaves as a potent antioxidant and neuroprotective compound. This research explores TMF's neuroprotective effects against Pb-induced brain toxicity in rats to establish it as a therapeutic agent. Rats received lead acetate (100 mg/kg, orally, once daily) for 30 days to induce brain injury, followed by TMF treatment (5 and 10 mg/kg, oral, once daily) 30 min later. Cognitive and motor functions were assessed using Morris Water Maze and horizontal bar tests. Lead, monoamine oxidase (MAO) A and B enzymes, reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), Tumor necrosis factor-alpha (TNF-α), and IL-6 levels were measured in the hippocampus and cerebellum. Pb exposure impaired cognitive and motor functions, increased Pb, TBARS, TNF-α, and IL-6 levels, and compromised MAO A & B and GSH levels. TMF reversed Pb-induced memory and motor deficits and normalized biochemical anomalies. TMF's neuroprotective effects against lead involve chelating, antioxidant, anti-inflammatory, and monoaminergic properties, suggesting its potential as a treatment for metal-induced brain injury.

A rare polyoxometalate cluster [NiW12O44]14- based solid as a pre-catalyst for efficient and long-term oxygen evolution.

Polyoxometalates (POMs) are an eminent class of metal oxide anionic clusters of early transition metals with huge structural diversity. Herein, a [NiW12O44]14- cluster based solid, (C5H7N2)6[NiW12O44], has been reported (PS-78). The [NiW12O44]14- cluster bridges the missing gap of 1 : 12 hetero-POMs of Keggin and Silverton together with a coordination number of 8 of the central heteroatom (Ni). Furthermore PS-78 has been explored as an efficient and highly sustained oxygen evolution pre-catalyst in alkaline medium with an overpotential of 347 mV to attain a current density of 10 mA cm-2 and long-term stability up to 96 hours. Furthermore, mechanistic investigation showed that in situ generated NiO and WO x (x = 1, 2) species act as active species for the oxygen evolution reaction. This study will open up new avenues for exploring POMs' new topologies and the potential of POMs as effective pre-catalysts in electrocatalytic applications.

Estimation of psychological stress in humans: a combination of theory and practice.

Stress has long been known to increase susceptibility to health disorders. In 2009, American Psychological Association further established association of stress to serious health problems. However, a quantitative and accurate way to evaluate and estimate stress status of individuals is still a big challenge. It has been shown, in large animal models using cattle, that psychological stress can be quantified as well as disease susceptibility could be predicted through biomarker discovery. Taking cue from those studies, we have evaluated and estimated psychological stress level of individuals theoretically and validated experimentally. Various biomarkers have also been identified which can be associated to psychological stress to predict stress status of unknown individuals.

Psychological stressors as interventions: good out of the evil.

Stress in general can be defined as a state of threatened balance, equilibrium or harmony that tends to disturb the homeostasis of the body. Stress can be of many kinds viz. psychological, physiological, social, emotional, and nutritional. Albeit the distinct kinds of stress stated in the aforementioned stress list, it is hard to bring out a clear distinction between them since each stress may precede or succeed the manifestation of any other. The studies discussed in the review elucidate effects of psychological stressors (PS) on diseases such as cancer, AIDS, epidermal abnormalities, obesity, and various inflammatory diseases like colonic inflammations, Coronary Artery Disease (CAD), Coronary Heart Disease (CHD), asthma. From these studies, further attempt was made to establish the basic mechanisms which come into play during a stressor stimulus and consequently modulate the physiology of the body. In this review we have highlighted effects of PS on diseases while simultaneously building on the modes of operation of PS to alter physiology and its further implications in developing potential psychotherapeutic methods for disease treatment.