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1.
Evol Appl ; 17(7): e13760, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39027688

ABSTRACT

Biological control of weeds involves deliberate introduction of host-specific natural enemies into invaded range to reduce the negative impacts of invasive species. Assessing the specificity is a crucial step, as introduction of generalist natural enemies into a new territory may pose risks to the recipient communities. A mechanistic understanding of host use can provide valuable insights for the selection of specialist natural enemies, bolster confidence in non-target risk assessment and potentially accelerate the host specificity testing process in biological control. We conducted a comprehensive analysis of studies on the genomics of host specialization with a view to examine if genomic signatures can help predict host specificity in insects. Focusing on phytophagous Lepidoptera, Coleoptera and Diptera, we compared chemosensory receptors and enzymes between "specialist" (insects with narrow host range) and "generalist" (insects with wide host range) insects. The availability of genomic data for biological control agents (natural enemies of weeds) is limited thus our analyses utilized data from pest insects and model organisms for which genomic data are available. Our findings revealed that specialists generally exhibit a lower number of chemosensory receptors and enzymes compared with their generalist counterparts. This pattern was more prominent in Coleoptera and Diptera relative to Lepidoptera. This information can be used to reject agents with large gene repertoires to potentially accelerate the risk assessment process. Similarly, confirming smaller gene repertoires in specialists could further strengthen the risk evaluation. Despite the distinctive signatures between specialists and generalists, challenges such as finite genomic data for biological control agents, ad hoc comparisons, and fewer comparative studies among congeners limit our ability to use genomic signatures to predict host specificity. A few studies have empirically compared phylogenetically closely related species, enhancing the resolution and the predictive power of genomics signatures thus suggesting the need for more targeted studies comparing congeneric specialists and generalists.

2.
Sci Rep ; 14(1): 11088, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750079

ABSTRACT

Many studies seeking to understand the success of biological invasions focus on species' escape from negative interactions, such as damage from herbivores, pathogens, or predators in their introduced range (enemy release). However, much less work has been done to assess the possibility that introduced species might shed mutualists such as pollinators, seed dispersers, and mycorrhizae when they are transported to a new range. We ran a cross-continental field study and found that plants were being visited by 2.6 times more potential pollinators with 1.8 times greater richness in their native range than in their introduced range. Understanding both the positive and negative consequences of introduction to a new range can help us predict, monitor, and manage future invasion events.


Subject(s)
Introduced Species , Animals , Pollination , Mycorrhizae/physiology , Symbiosis , Plants , Seed Dispersal , Ecosystem
3.
Indian J Crit Care Med ; 28(3): 200-250, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38477011

ABSTRACT

End-of-life care (EOLC) exemplifies the joint mission of intensive and palliative care (PC) in their human-centeredness. The explosion of technological advances in medicine must be balanced with the culture of holistic care. Inevitably, it brings together the science and the art of medicine in their full expression. High-quality EOLC in the ICU is grounded in evidence, ethical principles, and professionalism within the framework of the Law. Expert professional statements over the last two decades in India were developed while the law was evolving. Recent landmark Supreme Court judgments have necessitated a review of the clinical pathway for EOLC outlined in the previous statements. Much empirical and interventional evidence has accumulated since the position statement in 2014. This iteration of the joint Indian Society of Critical Care Medicine-Indian Association of Palliative Care (ISCCM-IAPC) Position Statement for EOLC combines contemporary evidence, ethics, and law for decision support by the bedside in Indian ICUs. How to cite this article: Mani RK, Bhatnagar S, Butola S, Gursahani R, Mehta D, Simha S, et al. Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit. Indian J Crit Care Med 2024;28(3):200-250.

4.
Cardiovasc Res ; 119(15): 2522-2535, 2023 11 25.
Article in English | MEDLINE | ID: mdl-37739930

ABSTRACT

AIMS: Long QT syndrome type 2 (LQTS2) is associated with inherited variants in the cardiac human ether-à-go-go-related gene (hERG) K+ channel. However, the pathogenicity of hERG channel gene variants is often uncertain. Using CRISPR-Cas9 gene-edited hiPSC-derived cardiomyocytes (hiPSC-CMs), we investigated the pathogenic mechanism underlying the LQTS-associated hERG R56Q variant and its phenotypic rescue by using the Type 1 hERG activator, RPR260243. METHODS AND RESULTS: The above approaches enable characterization of the unclear causative mechanism of arrhythmia in the R56Q variant (an N-terminal PAS domain mutation that primarily accelerates channel deactivation) and translational investigation of the potential for targeted pharmacologic manipulation of hERG deactivation. Using perforated patch clamp electrophysiology of single hiPSC-CMs, programmed electrical stimulation showed that the hERG R56Q variant does not significantly alter the mean action potential duration (APD90). However, the R56Q variant increases the beat-to-beat variability in APD90 during pacing at constant cycle lengths, enhances the variance of APD90 during rate transitions, and increases the incidence of 2:1 block. During paired S1-S2 stimulations measuring electrical restitution properties, the R56Q variant was also found to increase the variability in rise time and duration of the response to premature stimulations. Application of the hERG channel activator, RPR260243, reduces the APD variance in hERG R56Q hiPSC-CMs, reduces the variability in responses to premature stimulations, and increases the post-repolarization refractoriness. CONCLUSION: Based on our findings, we propose that the hERG R56Q variant leads to heterogeneous APD dynamics, which could result in spatial dispersion of repolarization and increased risk for re-entry without significantly affecting the average APD90. Furthermore, our data highlight the antiarrhythmic potential of targeted slowing of hERG deactivation gating, which we demonstrate increases protection against premature action potentials and reduces electrical heterogeneity in hiPSC-CMs.


Subject(s)
Ether-A-Go-Go Potassium Channels , Long QT Syndrome , Humans , Ether-A-Go-Go Potassium Channels/genetics , Long QT Syndrome/genetics , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/prevention & control , Myocytes, Cardiac , Action Potentials , Ethers , ERG1 Potassium Channel/genetics
5.
J Anaesthesiol Clin Pharmacol ; 39(2): 312-316, 2023.
Article in English | MEDLINE | ID: mdl-37564866

ABSTRACT

The quest for an effective regional anaesthesia technique in breast surgery has always been eluded by its apparent complexity. Various techniques had been described as anaesthetic techniques for breast cancer surgeries. Fascial plane blocks had been used as analgesic techniques for this procedure. We describe a case series of 12 patients who were given a combination of erector spinae plane block (ESP), Pectoralis I (Pecs I) and serratus anterior plane (SAP) block as sole anaesthetic technique with high risk surgical morbidity. Two patients had discomfort during retraction of axillary apex towards the end of surgery, and one patient had discomfort during medial parasternal incision, which needed a single bolus of low dose ketamine injection. Combined fascial plane blocks could be effectively utilized as a sole regional anesthesia modality for breast cancer surgeries with mild sedation.

6.
Proc Biol Sci ; 290(2005): 20231022, 2023 08 30.
Article in English | MEDLINE | ID: mdl-37583319

ABSTRACT

When a plant is introduced to a new ecosystem it may escape from some of its coevolved herbivores. Reduced herbivore damage, and the ability of introduced plants to allocate resources from defence to growth and reproduction can increase the success of introduced species. This mechanism is known as enemy release and is known to occur in some species and situations, but not in others. Understanding the conditions under which enemy release is most likely to occur is important, as this will help us to identify which species and habitats may be most at risk of invasion. We compared in situ measurements of herbivory on 16 plant species at 12 locations within their native European and introduced Australian ranges to quantify their level of enemy release and understand the relationship between enemy release and time, space and climate. Overall, plants experienced approximately seven times more herbivore damage in their native range than in their introduced range. We found no evidence that enemy release was related to time since introduction, introduced range size, temperature, precipitation, humidity or elevation. From here, we can explore whether traits, such as leaf defences or phylogenetic relatedness to neighbouring plants, are stronger indicators of enemy release across species.


Subject(s)
Ecosystem , Plants , Phylogeny , Australia , Herbivory , Introduced Species
7.
Indian J Anaesth ; 67(Suppl 1): S53-S59, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37065946

ABSTRACT

Background and Aims: Ipsilateral shoulder pain (ISP) post-thoracotomy impairs the recovery in early postoperative period, the aetiology of which is unclear. We studied to find out the incidence and risk factors associated with ISP. Methods: We did a prospective observational study, wherein 296 patients scheduled for thoracic surgeries were enroled. Pain in the shoulder during activity was assessed using American Shoulder and Elbow Surgeons standardised assessment method. All potential predictors were analysed in a multivariable penalised logistic regression model, using ISP as the outcome variable. Results: Of the 296 patients, 118 (39.8%) patients developed ISP. Of the 296 patients, 170 patients underwent thoracotomy and 110 underwent video-assisted thoracoscopic surgeries. The incidence of ISP was higher in thoracotomy patients (45.29%) compared to video-assisted thoracoscopic surgeries (32.7%). Majority of patients (43.2%) were aged more than 65 years, which was statistically significant as per univariate analysis (P = .007). The incidence of ISP was the highest at 41.89% among those who had lung cancer (n = 74), with disease involving right upper lobe and left upper lobe, 29% and 25.8%, respectively. The pain severity was moderate in 27.1% of patients during shoulder movements. Among the patients who had ISP, 77.1% expressed it as dull aching, whereas 21.2% described it as stabbing in nature. Conclusion: The incidence of ISP in those who underwent thoracic surgery was high and dull aching in nature, of mild to moderate intensity, commonly located on the posterior aspect of the shoulder. It was more common in those who underwent thoracotomy and more than 65 years of age.

8.
bioRxiv ; 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-37066380

ABSTRACT

Both innate and adaptive immunity are the important components of the human defense system against various diseases including cancer. Human Beta Defensin (hBD-1) is one such immunomodulatory peptide which is lost at high frequencies in malignant cancers, while high levels of expression are maintained in benign regions making it a potential biomarker for the onset and metastasis of the disease. Loss of putative function of hBD-1 as a tumor suppressor gene combined with the defects in apoptosis pathways (CD95, ASK1) make tumor cells insensitive to chemotherapy and render it ineffective. Triple negative breast cancer (TNBC) is an aggressive form of breast cancer for which no targeted therapy works due to lack of biomarkers (ER, PR and HER2 negative). That makes chemotherapy as a first line of treatment despite high side effects. TNBC is known for avoiding immunosurveillance and desensitizing themselves to intervention by dysregulating cell death pathways (CD95 & ASK1) and developing resistance to chemotherapy A priori Activation of Apoptosis Pathways of Tumor often referred to as AAAPT is a novel targeted tumor sensitizing technology which sensitizes low responsive and resistant tumor cells to evoke a better response from the current treatments for TNBC. Here, we show that hBD-1 is shown to target tumor specific biomarker Trx, activates dual cell death pathways CD95 and ASK1 (apoptosis stimulating kinase) to sensitize TNBC cells to chemotherapy drug Doxorubicin. As far as we know, this is the first-time injection of hBD-1 in TNBC mouse model to prove the restoration of hBD-1 back to the basal level can sensitize cancer cells which resulted in significant reduction of tumor volume in TNBC mouse modelâ€Ëœ in vivo. Sensitizing the low or non-responsive tumor cells by AAAPT and making chemotherapy work at lower doses may lead to the significant reduction of dose related side effects and may expand the therapeutic index of the current treatments.

9.
ACS Pharmacol Transl Sci ; 6(3): 372-386, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36926453

ABSTRACT

Traditional drug design focuses on specific biological targets where specific receptors or biomarkers are overexpressed by cancer cells. Cancer cells circumvent the interventions by activating survival pathways and/or downregulating cell death pathways for their survival. A priori activation of apoptosis pathways of tumor (AAAPT) is a novel tumor-sensitizing technology that sensitizes tumor cells that are not responding well to the current treatments by targeting specific survival pathways involved in the desensitization of tumor cells and tries to revive them selectively in cancer cells, sparing normal cells. Several vitamin E derivatives (AMP-001, AMP-002, AMP-003, and AMP-004) were synthesized, characterized, and studied for their anti-tumorigenic properties and their synergistic potential with the standard chemotherapy doxorubicin in various cancer cells including brain cancer stem cells in vitro. Preliminary studies revealed that AAAPT drugs (a) reduced the invasive potential of brain tumor stem cells, (b) synergized with Federal Drug Application-approved doxorubicin, and (c) enhanced the therapeutic index of doxorubicin in the triple-negative breast cancer tumor rat model, preserving the ventricular function compared to cardiotoxic doxorubicin alone at therapeutic dose. The AAAPT approach has the advantage of inhibiting survival pathways and activating cell death pathways selectively in cancer cells by using targeting, linkers cleavable by tumor-specific Cathepsin B, and PEGylation technology to enhance the bioavailability. We propose AAAPT drugs as a neoadjuvant to chemotherapy and not as stand-alone therapy, which is shown to be effective in expanding the therapeutic index of doxorubicin and making it work at lower doses.

10.
Phys Rev Lett ; 130(2): 026001, 2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36706394

ABSTRACT

A pair density wave (PDW) is a superconductor whose order parameter is a periodic function of space, without an accompanying spatially uniform component. Since PDWs are not the outcome of a weak-coupling instability of a Fermi liquid, a generic pairing mechanism for PDW order has remained elusive. We describe and solve models having robust PDW phases. To access the intermediate coupling limit, we invoke large-N limits of Fermi liquids with repulsive BCS interactions that admit saddle point solutions. We show that the requirements for long-range PDW order are that the repulsive BCS couplings must be nonmonotonic in space and that their strength must exceed a threshold value. We obtain a phase diagram with both finite temperature transitions to PDW order and a T=0 quantum critical point, where non-Fermi liquid behavior occurs.

11.
Indian J Anaesth ; 67(12): 1051-1060, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38343679

ABSTRACT

Background and Aims: Cancer pain guidelines remain confined due to implementation barriers, preventing them from attaining a global perspective. The guidelines must be robust in development and inculcate high-quality content to achieve practical utility. Quality indicators related to safe opioid practice empower effective guideline implementation. Methods: The protocol was registered prospectively in PROSPERO (CRD42021244823). Guidelines published over the last decade providing insights into cancer pain management and incorporating safe opioid practice were evaluated. The review's primary outcome was to evaluate the quality of cancer pain guidelines. Appraisal of guidelines for research and evaluation II (AGREE II) instrument was used to assess a guideline's quality. The ADAPTE collaboration-guideline adaptation resource tool kit (ADAPTE) provided insights into its adaptation based on specific questions within the guideline. Results: Fourteen cancer pain guidelines met the eligibility criteria and were included for quality evaluation. Eight guidelines were evaluated with combined AGREE II and ADAPTE process, attaining >66.7% in the rigour of development domain score, summated scaled domain score, and specific ADAPTE tools to evaluate the quality of each guideline. The intra-class correlation coefficient was utilised for resolving inter-rater agreement. 'Safe opioid practice' within a guideline was assessed for quality content implementation. Conclusion: Combined AGREE II and ADAPTE identified four cancer pain guidelines, namely Ministry of Health Malaysia, National Comprehensive Cancer Network, NCEC-National Clinical Guideline, and World Health Organization, which were of the highest quality and incorporated safe opioid practice effectively.

12.
Eur Heart J ; 43(45): 4739-4750, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36200607

ABSTRACT

AIMS: In response to pro-fibrotic signals, scleraxis regulates cardiac fibroblast activation in vitro via transcriptional control of key fibrosis genes such as collagen and fibronectin; however, its role in vivo is unknown. The present study assessed the impact of scleraxis loss on fibroblast activation, cardiac fibrosis, and dysfunction in pressure overload-induced heart failure. METHODS AND RESULTS: Scleraxis expression was upregulated in the hearts of non-ischemic dilated cardiomyopathy patients, and in mice subjected to pressure overload by transverse aortic constriction (TAC). Tamoxifen-inducible fibroblast-specific scleraxis knockout (Scx-fKO) completely attenuated cardiac fibrosis, and significantly improved cardiac systolic function and ventricular remodelling, following TAC compared to Scx+/+ TAC mice, concomitant with attenuation of fibroblast activation. Scleraxis deletion, after the establishment of cardiac fibrosis, attenuated the further functional decline observed in Scx+/+ mice, with a reduction in cardiac myofibroblasts. Notably, scleraxis knockout reduced pressure overload-induced mortality from 33% to zero, without affecting the degree of cardiac hypertrophy. Scleraxis directly regulated transcription of the myofibroblast marker periostin, and cardiac fibroblasts lacking scleraxis failed to upregulate periostin synthesis and secretion in response to pro-fibrotic transforming growth factor ß. CONCLUSION: Scleraxis governs fibroblast activation in pressure overload-induced heart failure, and scleraxis knockout attenuated fibrosis and improved cardiac function and survival. These findings identify scleraxis as a viable target for the development of novel anti-fibrotic treatments.


Subject(s)
Heart Failure , Ventricular Remodeling , Mice , Animals , Fibrosis , Myofibroblasts/metabolism , Cardiomegaly/metabolism , Fibroblasts/metabolism , Heart Failure/pathology , Myocardium/pathology , Mice, Inbred C57BL
13.
3 Biotech ; 12(10): 281, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36275360

ABSTRACT

Brown spot disease, caused by Bipolaris oryzae, is one of the several disastrous diseases affecting rice. The brown spot fungus illustrates substantial pathogenic and genetic variability. To the best of our knowledge, extensive analysis utilizing specific SSR primers for B. oryzae genome is quite inadequate for the population structure and genetic diversity of Indian B. oryzae isolates. A total of 84 brown spot isolates were collected from rice-cultivating areas across southern and eastern Indian states, viz., Tamil Nadu, Andhra Pradesh, Odisha and Chhattisgarh. The pathogenicity and virulence characteristics of these isolates were assessed with the susceptible cultivar CR Dhan 201. Twelve genome-specific SSR markers of B. oryzae warranted the investigation of the population structure and genetic diversity among the isolates. These isolates were categorized based on their disease grade as highly virulent isolates (4 nos.), virulent isolates (8 nos.), moderately virulent isolates (47 nos.) and less virulent isolates (25 nos.). PCR amplification and DNA sequencing confirmed the isolates to be B. oryzae. PCR amplification and DNA sequencing confirmed the isolates to be B. oryzae. The SSR markers produced a total of 35 alleles with 1 to 4 alleles per locus with a gene diversity ranging between 0.00 and 0.687 and a major allele frequency variation of 0.425-0.975. The PIC value ranged from 0.00 to 0.638 having a mean value of 0.34. Cluster analysis technique was applied to group the brown spot isolates into four distinct clusters. Principal coordinate and structure analysis identified two genetic clusters of B. oryzae isolates for individual states with some degree of distinctness complying with their virulence. Analysis of molecular variance revealed more genetic variation within populations and less among populations. The study outcome would expedite the comprehension of genetic diversity of B. oryzae across the southern and eastern states of India. Furthermore, we anticipate its guidance in the development of more effective disease management strategies as well as in the generation of novel resistant varieties through marker-assisted breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03347-4.

14.
Biol Lett ; 18(10): 20220220, 2022 10.
Article in English | MEDLINE | ID: mdl-36259169

ABSTRACT

Introduced species often benefit from escaping their enemies when they are transported to a new range, an idea commonly expressed as the enemy release hypothesis. However, species might shed mutualists as well as enemies when they colonize a new range. Loss of mutualists might reduce the success of introduced populations, or even cause failure to establish. We provide the first quantitative synthesis testing this natural but often overlooked parallel of the enemy release hypothesis, which is known as the missed mutualist hypothesis. Meta-analysis showed that plants interact with 1.9 times more mutualist species, and have 2.3 times more interactions with mutualists per unit time in their native range than in their introduced range. Species may mitigate the negative effects of missed mutualists. For instance, selection arising from missed mutualists could cause introduced species to evolve either to facilitate interactions with a new suite of species or to exist without mutualisms. Just as enemy release can allow introduced populations to redirect energy from defence to growth, potentially evolving increased competitive ability, species that shift to strategies without mutualists may be able to reallocate energy from mutualism toward increased competitive ability or seed production. The missed mutualist hypothesis advances understanding of the selective forces and filters that act on plant species in the early stages of introduction and establishment and thus could inform the management of introduced species.


Subject(s)
Plants , Symbiosis , Introduced Species
15.
J Anaesthesiol Clin Pharmacol ; 38(Suppl 1): S46-S51, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36060192

ABSTRACT

Background and Aims: COVID-19 has necessitated restrictions on elective surgical workload, which could adversely affect the learning of the core clinical competencies of the postgraduate anesthesiology trainees. The aim was to assess and compare the loss of elective cases requiring anesthesia management and associated procedural skills in six months since lockdown compared to the same duration in 2019. Material and Methods: We compared the data, obtained from electronic medical records, of the total number of elective surgeries requiring anesthesia management and the following procedural skills in both adults and pediatric patients in 6 months duration in 2019 and 2020: 1) Laryngoscopy and Intubation 2) Laryngeal mask airway 3) Arterial and central line cannulations and 4) Spinal, Epidural, Other Regional blocks. Results: A total of 8458 and 3561 elective procedures were performed in the six-month period in 2019 and 2020 respectively, reflecting a 57.9% reduction due to lockdown. There was a proportionate reduction in the adult and pediatric procedures, operating room and non-operating room procedures, and surgeries performed under general anesthesia and monitored anesthesia care. There was a significant increase in the number of surgeries performed under regional anesthesia (486%). Epidurals blocks and other regional blocks also showed a proportionate reduction respectively. Although the total number of video-laryngoscopy assisted intubations show an absolute reduction, when compared to the total number of cases performed in the respective years, we found an increase (2.06% in 2019 vs 3.8% in 2020). The arterial cannulations reduced by 43.29% but the central line cannulations reduced by only 12.28%. Conclusion: There was a significant reduction in both the anesthesia management opportunities and in the total number of associated procedural skills due to COVID-19 lockdown which could adversely affect the learning of core clinical competencies of postgraduate trainees.

16.
Cells ; 11(9)2022 04 27.
Article in English | MEDLINE | ID: mdl-35563778

ABSTRACT

Fibrosis is an energy-intensive process requiring the activation of fibroblasts to myofibroblasts, resulting in the increased synthesis of extracellular matrix proteins. Little is known about the transcriptional control of energy metabolism in cardiac fibroblast activation, but glutaminolysis has been implicated in liver and lung fibrosis. Here we explored how pro-fibrotic TGFß and its effector scleraxis, which drive cardiac fibroblast activation, regulate genes involved in glutaminolysis, particularly the rate-limiting enzyme glutaminase (GLS1). The GLS1 inhibitor CB-839 attenuated TGFß-induced fibroblast activation. Cardiac fibroblast activation to myofibroblasts by scleraxis overexpression increased glutaminolysis gene expression, including GLS1, while cardiac fibroblasts from scleraxis-null mice showed reduced expression. TGFß induced GLS1 expression and increased intracellular glutamine and glutamate levels, indicative of increased glutaminolysis, but in scleraxis knockout cells, these measures were attenuated, and the response to TGFß was lost. The knockdown of scleraxis in activated cardiac fibroblasts reduced GLS1 expression by 75%. Scleraxis transactivated the human GLS1 promoter in luciferase reporter assays, and this effect was dependent on a key scleraxis-binding E-box motif. These results implicate scleraxis-mediated GLS1 expression as a key regulator of glutaminolysis in cardiac fibroblast activation, and blocking scleraxis in this process may provide a means of starving fibroblasts of the energy required for fibrosis.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Glutaminase , Pulmonary Fibrosis , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Fibroblasts/metabolism , Glutaminase/genetics , Mice , Myofibroblasts/metabolism , Pulmonary Fibrosis/metabolism , Transforming Growth Factor beta/metabolism
17.
Cell Mol Life Sci ; 79(4): 193, 2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35298717

ABSTRACT

Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer's disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1 in neuroprotection has not been well established. We therefore used in vitro cell culture systems and animal models of diabetic neuropathy to characterize endogenous IGF-1 in sensory neurons and determine the factors regulating IGF-1 expression and/or affecting neuronal health. Single-cell RNA sequencing (scRNA-Seq) and in situ hybridization analyses revealed high expression of endogenous IGF-1 in non-peptidergic neurons and satellite glial cells (SGCs) of dorsal root ganglia (DRG). Brain cortex and DRG had higher IGF-1 gene expression than sciatic nerve. Bidirectional transport of IGF-1 along sensory nerves was observed. Despite no difference in IGF-1 receptor levels, IGF-1 gene expression was significantly (P < 0.05) reduced in liver and DRG from streptozotocin (STZ)-induced type 1 diabetic rats, Zucker diabetic fatty (ZDF) rats, mice on a high-fat/ high-sugar diet and db/db type 2 diabetic mice. Hyperglycemia suppressed IGF-1 gene expression in cultured DRG neurons and this was reversed by exogenous IGF-1 or the aldose reductase inhibitor sorbinil. Transcription factors, such as NFAT1 and CEBPß, were also less enriched at the IGF-1 promoter in DRG from diabetic rats vs control rats. CEBPß overexpression promoted neurite outgrowth and mitochondrial respiration, both of which were blunted by knocking down or blocking IGF-1. Suppression of endogenous IGF-1 in diabetes may contribute to neuropathy and its upregulation at the transcriptional level by CEBPß can be a promising therapeutic approach.


Subject(s)
Aging/metabolism , Axons/pathology , CCAAT-Enhancer-Binding Protein-beta/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Energy Metabolism , Insulin-Like Growth Factor I/metabolism , Sensory Receptor Cells/metabolism , Animals , Antibodies, Neutralizing/pharmacology , Axons/drug effects , Axons/metabolism , Base Sequence , CCAAT-Enhancer-Binding Protein-beta/genetics , Cell Respiration/drug effects , Cells, Cultured , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Energy Metabolism/drug effects , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Gene Expression Regulation/drug effects , Glycolysis/drug effects , HEK293 Cells , Humans , Insulin-Like Growth Factor I/genetics , Liver/metabolism , Male , Mitochondria/drug effects , Mitochondria/metabolism , NFATC Transcription Factors/metabolism , Neuronal Outgrowth/drug effects , Polymers/metabolism , Promoter Regions, Genetic/genetics , Protein Transport/drug effects , Rats, Sprague-Dawley , Sensory Receptor Cells/pathology , Signal Transduction/drug effects
18.
Nanoscale ; 14(11): 4312-4323, 2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35253034

ABSTRACT

Blister packing materials (BMs) made up of foamed plastics are one of the major components in consumer goods, pharmaceuticals, and medical devices, which lead to a serious environmental concern as the waste management processes often result in land filling and incineration. The effective recycling of these foamed plastics has turned out to be a topic of interest in recent years to address environmental issues. Under stipulated experimental conditions, the foamed plastic of blister packaging materials, consisting of a higher percentage of carbon can provide an efficient anode material for energy storage devices. The present work outlines the preparation steps of defect-engineered graphene-like turbostratic carbon via. a physico-chemical activation method resulting in the formation of ultralow surface area (∼11.4 m2 g-1) carbon materials. In addition, graphene-like wrinkled morphologies were found to exist in the carbonaceous materials prepared at higher activation temperature (∼1400 °C) with a notable change in the crystalline characteristics on par with the commercial graphite anode. Therefore, it is expected that the material could be used in the same manner as conventional graphite materials to fabricate the cells. The prepared carbon, when explored as a lithium-ion battery (Li-ion) anode, provided outstanding electrochemical properties with a noteworthy Li-ion storage capacity of 594 mA h g-1 measured at a current rate of 0.1 C after 200 cycles, thanks to its graphene-like features, facilitating faster Li+ diffusion. Even at a high C-rate (1 C), the waste plastic-derived carbon displayed outstanding rate performance (∼304 mA h g-1) with noteworthy capacity retention (∼89%) and enhanced cycling stability (over 2000 cycles). Thus, the present research paves a new route for generating value-added carbon materials using foamed plastic med-wastes derived from blister packs.

19.
Chemosphere ; 288(Pt 1): 132438, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34619259

ABSTRACT

The uncontrolled accumulation of end-of-life tires every year leads to serious environmental concerns, rendering setback to the sustainable growth of the society. The most viable solution to overcome this environmental issue is to convert these hazardness waste tires into value added products. In the present investigation, carbonecous based anode materials has been developed by a novel chemical activation strategy involving aqua regia followed by controlled pyrolytic condition in the selective atmospheres. Raman spectroscopic study displayed a graphitic carbon with significant degree of disordered arrangements. The generation of the turbostratic carbon with higher content of broken crystal edges is corroborated using the structural characterization such as X-ray diffraction (XRD). This fact is further corroborated from surface energy results calculated using the contact angles measured by dynamic wicking method. The prepared turbostratic carbon, when used as lithium anode, renders excellent electrochemical performances with reversible specific capacity of 350 mAhg-1 (at 300 mAg-1) with 81% capacity retention after 500 cycles. The present research provides new roadmap in recycling the waste tires for energy storage applications.


Subject(s)
Carbon , Lithium , Electric Power Supplies , Electrodes , Recycling
20.
J Opioid Manag ; 17(5): 417-437, 2021.
Article in English | MEDLINE | ID: mdl-34714542

ABSTRACT

Opioids are an indispensable part of perioperative pain management of cancer surgeries. Opioids do have some side effects and abuse potential, and some laboratory data suggest a possible association of cancer recurrence with perioperative opioid use. Opioid-free anesthesia and opioid-sparing anesthesia are emerging new concepts worldwide to safeguard patients from adverse effects of opioids and potential abuse. Opioid-free anesthesia could lead to ineffective pain management, leaving the perioperative physician with limited options, while opioid-sparing anesthesia may be a rational approach. This consensus guideline includes general considerations of the safe use of perioperative opioids along with concomitant use of central neuraxial or regional blockade and systematic nonopioid analgesics. Region-specific onco-surgeries with their specific recommendations and consensus statements for judicious use of opioids are suggested. Use of epidural analgesia or regional catheter during thoracic, abdominal, pelvic, and lower limb surgeries and use of regional nerve blocks/catheter in head neck, neuro, and upper limb onco-surgeries, wherever possible along with nonopioids analgesics, are suggested. Short-acting opioids in small aliquots may be allowed to control breakthrough pain for expedient control of pain. The purpose of this consensus practice guideline is to provide the practicing anesthesiologists with best practice evidence and consensus recommendations by the expert committee of the Society of Onco-Anesthesia and Perioperative Care for safe opioid use in onco-surgeries.


Subject(s)
Analgesics, Opioid , Anesthesia , Analgesics, Opioid/adverse effects , Humans , Pain Management , Pain, Postoperative/diagnosis , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Perioperative Care
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