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BACKGROUND: 22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways. METHODS: We analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2. We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions, testing case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation. RESULTS: BSV, LC, and GBC are significantly disrupted in 22qDel compared with TD controls (False Discovery Rate q<0.05). Spatial maps of BSV and LC differences are highly correlated with each other, unlike GBC. In CHR, only LC is significantly altered versus controls, with a different spatial pattern compared to 22qDel. Group differences map onto biological gradients, with 22qDel effects strongest in regions with high predicted blood flow and metabolism. CONCLUSION: 22qDel and CHR exhibit divergent effects on fMRI temporal variability and multi-scale functional connectivity. In 22qDel, strong and convergent disruptions in BSV and LC not seen in CHR individuals suggest distinct functional brain alterations.
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The P-type ATPase superfamily genes are the cation and phospholipid pumps that transport ions across the membranes by hydrolyzing ATP. They are involved in a diverse range of functions, including fundamental cellular events that occur during the growth of plants, especially in the reproductive organs. The present work has been undertaken to understand and characterize the P-type ATPases in the pigeonpea genome and their potential role in anther development and pollen fertility. A total of 59 P-type ATPases were predicted in the pigeonpea genome. The phylogenetic analysis classified the ATPases into five subfamilies: eleven P1B, eighteen P2A/B, fourteen P3A, fifteen P4, and one P5. Twenty-three pairs of P-type ATPases were tandemly duplicated, resulting in their expansion in the pigeonpea genome during evolution. The orthologs of the reported anther development-related genes were searched in the pigeonpea genome, and the expression profiling studies of specific genes via qRT-PCR in the pre- and post-meiotic anther stages of AKCMS11A (male sterile), AKCMS11B (maintainer) and AKPR303 (fertility restorer) lines of pigeonpea was done. Compared to the restorer and maintainer lines, the down-regulation of CcP-typeATPase22 in the post-meiotic anthers of the male sterile line might have played a role in pollen sterility. Furthermore, the strong expression of CcP-typeATPase2 in the post-meiotic anthers of restorer line and CcP-typeATPase46, CcP-typeATPase51, and CcP-typeATPase52 in the maintainer lines, respectively, compared to the male sterile line, clearly indicates their potential role in developing male reproductive organs in pigeonpea.
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Cajanus , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Pólen , Pólen/genética , Pólen/crescimento & desenvolvimento , Cajanus/genética , Cajanus/crescimento & desenvolvimento , Cajanus/enzimologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ATPases do Tipo-P/genética , ATPases do Tipo-P/metabolismo , Fertilidade/genética , Flores/genética , Flores/crescimento & desenvolvimento , Infertilidade das Plantas/genética , Perfilação da Expressão Gênica , Genoma de PlantaRESUMO
This study examines the effectiveness of lupeol and metformin in a mouse model of dementia generated by intracerebroventricular streptozotocin (i.c.v., STZ). Dementia was induced in Swiss mice with the i.c.v. administration of STZ at a dosage of 3 mg/kg on the first and third day. The assessment of dementia involved an examination of the Morris Water Maze (MWM) performance, as well as a number of biochemical and histological studies. STZ treatment resulted in significant decrease in MWM performance; various biochemical alterations (increase in brain acetyl cholinesterase (AChE) activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate, and reduction in nuclear factor erythroid 2 related factor-2 (Nrf-2), reduced glutathione (GSH) levels) and neuroinflammation [increased myeloperoxidase (MPO) activity & neutrophil infiltration]. The administration of Lupeol (50 mg/kg & 100 mg/kg; p.o.) and Metformin (150 mg/kg & 300 mg/kg; p.o.) demonstrated a considerable reduction in the behavioral, biochemical, and histological alterations produced by STZ. Low dose combination of lupeol (50 mg/kg; p.o.) and Metformin (150 mg/kg; p.o.) produced more pronounced effect than that of high doses of either agent alone. It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type.
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Demência , Modelos Animais de Doenças , Metformina , Triterpenos Pentacíclicos , Estreptozocina , Animais , Triterpenos Pentacíclicos/uso terapêutico , Triterpenos Pentacíclicos/farmacologia , Metformina/farmacologia , Metformina/uso terapêutico , Estreptozocina/toxicidade , Camundongos , Demência/tratamento farmacológico , Demência/induzido quimicamente , Masculino , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Glutationa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , LupanosRESUMO
To unravel the plastid genome diversity among the cultivated groups of the pigeonpea germplasm, we characterized the SNP occurrence and distribution of 142 pigeonpea mini-core collections based on their reference-based assembly of the chloroplast genome. A total of 8921 SNPs were found, which were again filtered and finally 3871 non-synonymous SNPs were detected and used for diversity estimates. These 3871 SNPs were classified into 12 groups and were present in only 44 of the 125 genes, demonstrating the presence of a precise mechanism for maintaining the whole chloroplast genome throughout evolution. The Acetyl-CoA carboxylase D gene possesses the maximum number of SNPs (12.29%), but the Adenosine Tri-Phosphate synthatase cluster genes (atpA, atpB, atpE, atpF, atpH, and atpI) altogether bear 43.34% of the SNPs making them most diverse. Various diversity estimates, such as the number of effective alleles (1.013), Watterson's estimate (0.19), Tajima's D ( - 3.15), Shannon's information index (0.036), suggest the presence of less diversity in the cultivated gene pool of chloroplast genomes. The genetic relatedness estimates based on pairwise correlations were also in congruence with these diversity descriptors and indicate the prevalence of rare alleles in the accessions. Interestingly, no stratification was observed either through STRUCTURE, PCoA, or phylogenetic analysis, indicating the common origin of the chloroplast in all the accessions used, irrespective of their geographical distribution. Further 6194 Cleaved Amplified Polymorphic Sequences (CAPS) markers for 531 SNPs were developed and validated in a selected set of germplasm. Based on these results, we inferred that all of the cultivated gene pools of pigeonpea have a common origin for the chloroplast genome and they possess less diversity in protein-coding regions, indicating a stable and evolved plastid genome. At the same time, all diversity analysis indicates the occurrence of rare alleles, suggesting the suitability of the mini-core collection in future pigeonpea improvement programs. In addition, the development of chloroplast genome-based CAPS markers would have utility in pigeonpea breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03785-8.
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Myocardial ischemic injury is a primary cause of death among various cardiovascular disorders. The condition occurs due to interrupted blood supply and vital nutrients (necessary for normal cellular activities and viability) to the myocardium, eventually leading to damage. Restoration of blood supply to ischemic tissue is noted to cause even more lethal reperfusion injury. Various strategies, including some conditioning techniques like preconditioning & postconditioning have been developed to check detrimental effects of reperfusion injury. Many endogenous substances have been proposed to act as initiator, mediators and end effectors of these conditioning techniques. Substances like adenosine, bradykinin, acetylcholine, angiotensin, norepinephrine, opioids, etc., have been reported to mediate cardioprotective activity. Among these agents, adenosine has been widely studied and suggested to have the most pronounced cardioprotective effects. The current review article highlights the role of adenosine signaling in the cardioprotective mechanism of conditioning techniques. The article also provides an insight into various clinical studies that substantiate the applicability of adenosine as a cardioprotective agent in myocardial-reperfusion injury.
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All over the world, cancer death and prevalence are increasing. Breast cancer (BC) is the major cause of cancer mortality (15%) which makes it the most common cancer in women. BC is defined as the furious progression and quick division of breast cells. Novel nanotechnology-based approaches helped in improving survival rate, metastatic BC is still facing obstacles to treat with an expected overall 23% survival rate. This paper represents epidemiology, classification (non-invasive, invasive and metastatic), risk factors (genetic and non-genetic) and treatment challenges of breast cancer in brief. This review paper focus on the importance of nanotechnology-based nanoformulations for treatment of BC. This review aims to deliver elementary insight and understanding of the novel nanoformulations in BC treatment and to explain to the readers for enduring designing novel nanomedicine. Later, we elaborate on several types of nanoformulations used in tumor therapeutics such as liposomes, dendrimers, polymeric nanomaterials and many others. Potential research opportunities for clinical application and current challenges related to nanoformulations utility for the treatment of BC are also highlighted in this review. The role of artificial intelligence is elaborated in detail. We also confer the existing challenges and perspectives of nanoformulations in effective tumor management, with emphasis on the various patented nanoformulations approved or progression of clinical trials retrieved from various search engines.
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The aim of this study was to compare quilting suture with axillary drain versus conventional sutures with axillary and pectoral drain on the formation of seroma after modified radical mastectomy with axillary lymph node dissection. The study was undertaken among 90 female patients with breast cancer who were candidates for modified radical mastectomy with axillary clearance. The intervention group (N = 43) with quilting and axillary drain placement and the control group (N = 33) without quilting with axillary and pectoral drain placement. All the patients were followed up for complications pertaining to this procedure. There were no significant differences between the two groups with regard to demographic characteristics, comorbidities, pre-operative chemotherapy, post-operative pathological findings, lymph node involvement or clinical staging. The incidence of seroma formation on follow-up was significantly lower in the intervention group than that in the control group (23% versus 58%; p < 0.05) whereas there was no significant difference with respect to flap necrosis, superficial skin necrosis and wound gaping between the two groups. Furthermore, it took a shorter duration for seroma to resolve in the intervention group (4 days versus 9 days; p < 0.001) with a smaller duration of hospital stay (4 days versus 9 days; p < 0.001). The use of quilting sutures for flap fixation in order to obliterate dead space post-modified radical mastectomy with placement of axillary drain significantly reduced seroma formation along with shorter duration of wound drainage and a smaller hospital stay with only slightly increased operative time. Therefore, we recommend quilting of flap as a routine step after mastectomy.
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Myocardial ischemic injury is a primary cause of death among various cardiovascular disorders. The condition occurs due to an interrupted supply of blood and vital nutrients (necessary for normal cellular activities and viability) to the myocardium, eventually leading to damage. Restoration of blood supply to ischemic tissue is noted to cause even more lethal reperfusion injury. Various strategies, including some conditioning techniques, like preconditioning and postconditioning, have been developed to check the detrimental effects of reperfusion injury. Many endogenous substances have been proposed to act as initiators, mediators, and end effectors of these conditioning techniques. Substances, like adenosine, bradykinin, acetylcholine, angiotensin, norepinephrine, opioids, etc., have been reported to mediate cardioprotective activity. Among these agents, adenosine has been widely studied and suggested to have the most pronounced cardioprotective effects. The current review article highlights the role of adenosine signaling in the cardioprotective mechanism of conditioning techniques. The article also provides an insight into various clinical studies that substantiate the applicability of adenosine as a cardioprotective agent in myocardial reperfusion injury.
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Precondicionamento Isquêmico Miocárdico , Traumatismo por Reperfusão Miocárdica , Humanos , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio , Cardiotônicos/uso terapêutico , Cardiotônicos/farmacologia , Transdução de SinaisRESUMO
AIM: The study investigates the effect of Valsartan, an Angiotensin II type 1 receptor blocker (ARB), on the blunted neuroprotective response of ischemic post-conditioning (iPoCo) in rats subjected to High Fat Diet (HFD). BACKGROUND: The neuroprotective response of iPoCo is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolemia, diabetes, hypertension, etc. Objectives: The study was undertaken to investigate the effect of Valsartan, an ARB, on the blunted neuroprotective response of iPoCo in rats subjected to HFD. METHODS: Wistar rats were subjected to HFD for 56 days. The cerebral ischemic injury was induced by bilateral common carotid artery occlusion (BCCAO) for 12 min followed by reperfusion of 24 hrs. iPoCo was induced by three preceding cycles of ischemia and reperfusion lasting 1 min each given immediately after BCCAO at the onset of prolonged reperfusion. The extent of the injury was assessed in terms of memory impairment using the Morris Water Maze test (MWM), sensorimotor disturbance using the neurological severity score (NSS), and cerebral infarct size using triphenyl tetrazolium chloride staining. Series of biochemical estimations including brain thiobarbituric acid reactive species (TBARS); reduced glutathione (GSH); myeloperoxidase (MPO); tumor necrosis factor-α (TNF-α); Nrf-2 and serum cholesterol, serum nitrite levels were performed. RESULTS: BCCAO produced significant cerebral injury indicated by increased cerebral infarct size, memory impairment, increased NSS, and various biochemical alterations (increased cholesterol, TBARS, MPO, TNF-α, Nrf-2, and decreased nitrite and GSH levels). Significant neutrophil infiltration was also observed. iPoCo attenuated BCCAO-induced injury with respect to the above parameters in normal rats. The protective response of iPoCo was lost in HFD-treated rats. Treatment of Valsartan attenuated cerebral injury, potentiated the neuroprotective response of iPoCo in normal rats, and also restored the blunted neuroprotective effect of iPoCo in HFD-treated rats along with enhanced Nrf-2 levels. CONCLUSION: Valsartan exerted a neuroprotective effect by virtue of its multiple actions with a crucial role of Nrf2 activation.
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Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Valsartana , Dieta Hiperlipídica/efeitos adversos , Antagonistas de Receptores de Angiotensina , Nitritos , Substâncias Reativas com Ácido Tiobarbitúrico , Fator de Necrose Tumoral alfa , Ratos Wistar , Inibidores da Enzima Conversora de Angiotensina , Infarto Cerebral , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Transtornos da Memória , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/patologia , ColesterolRESUMO
Dahi samples were prepared from milk incorporated with spray-dried iron-whey protein concentrate (Fe-WPC) conjugate and ferrous sulfate (FeSO4) with three different concentrations of iron i.e. 15, 20 and 25 mg/L and their quality characteristics were determined. Fe-WPC conjugate incorporated dahi showed better sensory, textural and physical attributes as compared with those of FeSO4 fortified and control dahi. Non-significant (p > 0.05) changes were observed in attributes like acidity and flavor, color and appearance, body and texture scores of dahi fortified with Fe-WPC conjugate with upto 20 mg/L iron as compared to those of control. In contrast, definite metallic flavor was perceptible in case of FeSO4 incorporated dahi even at 15 mg/L level. Water holding capacity, viscosity and firmness were significantly (p < 0.05) higher in 20 mg/L Fe-WPC conjugate incorporated dahi samples as compared with those of 20 mg/L FeSO4 incorporated dahi samples. In vitro bio accessibility of iron from Fe-WPC conjugate incorporated dahi was found to be significantly (p < 0.05) higher than that from FeSO4 incorporated dahi. Therefore, the results indicated that Fe-WPC conjugate can be fortified in dahi with upto 20 mg/L without significantly altering its physicochemical properties and with a higher bioaccessibillity of iron.
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Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results: A total of 10â¯930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration: PROSPERO Identifier: CRD42021230155.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Interleucina-6/antagonistas & inibidores , Idoso , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Causas de Morte , Coinfecção , Progressão da Doença , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração ArtificialRESUMO
BACKGROUND: Cancer is one of the most dreaded diseases characterized by uncontrolled proliferation of abnormal cells that occurs due to impairment of cell division and apoptosis process. Cancer is categorized into several types on the basis of affected organs and breast cancer (BC) is the most predominant cause of mortality among women. Although, several synthetic and semi-synthetic therapies have been developed for the treatment of BC but they exhibit numerous serious adverse effects therefore; pharmacological agents with fewer/no side effects need to be explored. Plants and phytoconstituents perhaps fulfill the aforementioned requirement and could serve as a potential and alternative therapy for BC treatment. The ongoing biomedical research, clinical trials and number of patents granted have further boosted the acceptance of the plants and plant-derived constituents in the effective treatment of BC. PURPOSE OF STUDY: Various treatment strategies such as checkpoint inhibitors, targeting micro RNA, apoptotic pathway, BRCA-1 gene, P53 protein, P13K/Akt/mTOR pathway, notch signaling pathway, hedgehog/gli-1 signaling pathway, poly-ADP ribose polymerase inhibitors, mitogen-activated protein kinase inhibitors etc. are available for BC. In addition to these synthetic and semi-synthetic drug therapies, several natural constituents such as alkaloids, sesquiterpenes, polyphenols, flavonoids and diterpenoids from medicinal plants, vegetables and fruits are reported to possess promising anti-cancer activity. The purpose of the present review is to highlight the various signaling pathways through which plants/herbs show the anti-cancer potential especially against the BC. STUDY DESIGN: The literature for the present study was collected from various databases such as Pubmed, Scopus, Chemical Abstracts, Medicinal and aromatic plant abstracts, Web of Science etc. The different patent databases were also reviewed for the anti-cancer (BC) potential of the particular herbs/plants and their formulations. RESULT AND CONCLUSION: In this review, we have discussed the number of plants along with their patents of different herbal formulations which are being used for the treatment of BC and other types of cancers. We have also delineated the different signaling mechanisms through which they inhibit the growth of BC cells. In nutshell, we can conclude that large numbers of herbs or their extracts are reported for the treatment of BC. But still, there is further need for research in-depth to translate the use of natural products clinically BC treatment.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Feminino , Humanos , Fitoterapia , Plantas Medicinais/químicaRESUMO
BACKGROUND AND AIM: Veterinary health care is an emergent area in animal sciences and innovative therapeutic approaches happen to be imperative in the present days. In view of the importance of cattle health and production, it is necessary to take up contemporary approach of stem cell therapy in this sector also. This study aimed to standardize an explant culture method of bovine umbilical tissue offcut to isolate mesenchymal stem cells (MSCs) because considerable efforts are required for ensuring easy accessibility and availability of MSCs in bulk quantity, as well as in establishing and characterizing the cell lines. MATERIALS AND METHODS: The umbilical cord (UC) tissue matrix offcut was collected after calving. A simplified in vitro cell isolation technique was followed to collect the emerged out cells from the explants of UC. Further, we expanded these isolated cells in vitro, observed its growth kinetics, and characterized to confirm as per the criterion of bovine MSCs. RESULTS: A considerable exponential growth rate of the UC-derived cells was noticed. In addition to their confirmation as MSCs, the cells also exhibited plastic adherent property and maintained the spindle-shaped morphology throughout the in vitro culture. The cultured cells were found positive MSC-specific surface markers CD105, CD90, and CD73 and were negative for hematopoietic cell marker CD45. Cytochemical studies revealed the ability of the cells to differentiate into osteogenic, chondrogenic, and adipogenic lineages. CONCLUSION: This simplified method of isolation and culture of bovine multipotent MSCs from the UC offcut collected after calving could be extrapolated for the greater availability of the cells for prospective therapeutic applications.
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Nanotopography of culture substrate acts as a positive cue in cell-biomaterial based tissue regeneration. Considering the potentiality of carbon nanotubes (CNTs) this study was designed to evaluate its two functionalized form by an in vitro culture condition using canine mesenchymal stem cells as cellular model. Cells were isolated and its behaviour, proliferation and differentiation processes were elucidated onto CNT substrates. Beside the variations in cellular behaviour it was remarkably noted that even though proliferation was reduced but osteogenic and chondrogenic differentiation was enhanced over multi-walled CNTs, whereas neuronal differentiation was better supported by single walled CNTs as evidenced by our cytochemical, immunocytochemical, gene expression and flow cytometry assays. The former one was noticed more cytocompatible by our different apoptosis studies. The outcome of these experiments collectively indicated that hydroxylated functionalized CNTs could be a potential scaffold constituent for future experimentations as well as for the application in regenerative medicine.
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In the field of regenerative medicine, numerous potential applications of mesenchymal stem cells (MSCs) can be envisaged, due to their ability to differentiate into a range of tissues on the basis of the substrate on which they grow. With the advances in nanotechnology, carbon nanotubes (CNTs) have been widely explored for use as cell culture substrate in tissue engineering applications. In this study, canine bone marrow-derived MSCs were considered as the cellular model for an in vitro study to elucidate the collective cellular processes, using three different varieties of thin films of functionalized carbon nanotubes (COOH-single-walled CNTs [SWCNTs], COOH-multiwalled CNTs [MWCNTs] and polyethylene glycol [PEG]-SWCNTs), which were spray dried onto preheated cover slips. Cells spread out better on the CNT films, resulting in higher cell surface area and occurrence of filopodia, with parallel orientation of stress fiber bundles. Canine MSCs proliferated at a slower rate on all types of CNT substrates compared to the control, but no decline in cell number was noticed during the study period. Expression of apoptosis-associated genes decreased on the CNT substrates as time progressed. On flow cytometry after AnnexinV-fluorescein isothiocyanate/propidium iodide (PI) staining, total number of apoptotic and necrotic cells remained lower in COOH-functionalized films compared to PEG-functionalized ones. Collectively, these results indicate that COOH-MWCNT substrate provided an environment of low cytotoxicity. Canine MSCs were further induced to differentiate along osteogenic, chondrogenic, and neuronal lineages by culturing under specific differentiation conditions. The cytochemical and immunocytochemical staining results, as well as the expression of the bone marker genes, led us to hypothesize that the COOH-MWCNT substrate acted as a better cue, accelerating the osteogenic differentiation process. However, while chondrogenesis was promoted by COOH-SWCNT, neuronal differentiation was promoted by both COOH-SWNCT and COOH-MWCNT. Taken together, these findings suggest that COOH-functionalized CNTs represent a promising scaffold component for future utilization in the selective differentiation of canine MSCs in regenerative medicine.
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Células-Tronco Mesenquimais/citologia , Nanotubos de Carbono/química , Alicerces Teciduais , Animais , Apoptose/genética , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Diferenciação Celular/fisiologia , Condrogênese/fisiologia , Cães , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/fisiologia , Osteogênese/fisiologia , Polietilenoglicóis/química , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodosRESUMO
'Kinnow' is a hybrid mandarin, developed at California (USA) but could not become successful there. However, it revolutionized citrus industry in India, Pakistan and Bangladesh. Recent reports indicate that like other citrus fruits, it also suffers from juice-sac granulation but exact cause of this malady is not known. Fully-mature 'Kinnow' fruits were harvested and observations on some physical and biochemical attributes were recorded and their relationship was established with occurrence of granulation. About 12.8 % 'Kinnow' fruits were affected by juice-sac granulation. Granulated fruits had higher average weight (178 ± 2.26 g), peel thickness (3.72 ± 0.23 mm), and less soluble solids concentrates (7.4 ± 0.21 %) than non-granulated fruits. Granulated fruits exhibited lower concentrations of total phenolics compounds (4.3 ± 0.56 mg 100(-1) g gallic acid equivalent fresh weigh) and antioxidants activity (1.78 ± 0.29 µmol Trolox g(-1) FW) but produced higher rates of carbon dioxide and ethylene, and exhibited higher activities of senescent-related enzymes such as lipoxygenase (LOX) (1.3 ± 0.31 µmoles min(-1) g(-1) FW) and pectin methylesterase (PME) (0.52 ± 0.12 µmol of NaOH g(-1) FW min(-1)) and had strong relationships with the occurrence of granulation. From this study, it can be concluded that total phenolics compounds, antioxidants and PAL enzyme activity have strongly negative co-relation; whereas, senescent-related enzymes such as LOX, and PME and rates of respiration or ethylene evolution have strongly positive relationships with the occurrence of granulation in 'Kinnow' mandarin.
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Cord tissue fills the umbilical cord around the blood vessels and contains types of stem cells (mesenchymal stem cells or MSCs) that are not generally found in cord blood. MSCs are the stem cells that give rise to many of the "support tissues" in the body, including bone, cartilage, fat and muscle. Umbilical Cord Tissue cells (UCTs) possessing the capacity to differentiate into various cell types such as osteoblasts, chondrocytes and adipocytes have been previously isolated from different species including human, canine, murine, avian species etc. The present study documents the existence of similar multipotential stem cells in caprine UCTs having similar growth and morphological characteristics. The cells were isolated from caprine umbilical cord and cultivated in DMEM (low glucose) supplemented with 15% FBS, L-glutamine and antibiotics. Primary culture achieved confluence in 5-7days having spindle shaped morphology. The cells were morphologically homogeneous, showed robust proliferation ability with a population doubled time of 92.07h as well as normal karyotype. In vitro self-renewal capacity was demonstrated by colony-forming unit assay (CFU). The cells expressed MSC specific markers and showed multi-differentiation capability into adipogenic and osteogeneic. The results indicated that caprine UCTs (cUCTs) were isolated and characterized from umbilical cord tissue which can be used for tissue regeneration.
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Técnicas de Cultura de Células/métodos , Diferenciação Celular/genética , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Adipogenia/genética , Animais , Separação Celular , Cães , Cabras , Humanos , Osteogênese/genéticaRESUMO
Acute fibrinous and organizing pneumonia (AFOP) is a rare disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of "fibrin balls." Here, we report a 43-year-old female with complaints of fever, dry cough, and shortness of breath with hypoxemia. High-resolution computed tomography thorax revealed diffuse confluent consolidation in bilateral lung zones. Bronchoscopy and transbronchial biopsy revealed features of AFOP. With prednisolone treatment, there was an improvement in her condition. AFOP is a rare disease and should be taken into consideration and differential diagnosis of severe acute pneumonias with no significant comorbidities.
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Neural stem cells (NSCs) can self-renew and give rise to neurons, astrocytes and oligodendrocytes; they are found in the nervous system of mammalian organisms, representing a promising resource for both fundamental research and therapeutics. There have been few investigations on NSCs in the livestock species. Therefore, we have successfully isolated and characterised NSCs from the foetal brain of a small domestic animal, the goat (called GNSCs). These cells from the foetal brain showed self-renewal, rapid proliferation with a population doubling time of 88 h, were morphologically homogeneous and maintained normal chromosome throughout the culture period. The cells expressed NSC-specific markers (Sox2, Pax6 and Mushashi), but were negative for CD34 and CD45. They were capable of multi-differentiation into neurons, astrocytes, oligodendrocytes, as well as adipocytes and osteocytes. The availability of such cells may hold great interest for basic and applied neuroscience.
Assuntos
Células-Tronco Neurais/fisiologia , Animais , Antígenos de Diferenciação/metabolismo , Diferenciação Celular , Proliferação de Células , Separação Celular , Células Cultivadas , CabrasRESUMO
L-asparaginase (L-ASNase) is an enzyme used most effectively in the treatment of acute lymphoblastic leukemia (ALL) for more than 30 years. It catalyzes the hydrolysis of amino acid l-asparagine to aspartic acid and ammonia, which leads to cell death. Clinical trials have been conducted using L-ASNase in combination with other drugs and radiotherapy, which have led to great success in the treatment of ALL. Treatments consist of induction therapy and central nervous system therapy. The achievement of complete remission in patients is associated with a few side-effects of using L-asparaginase, including pancreatitis, coagulation abnormalities and allergic reactions. Sometimes tumor cells may develop resistance to L-ASNase. To overcome these difficulties, the drug is modified by pegylation or immobilization, and also treatment protocols can be modified to increase the efficiency of the drug.