Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,de...Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.展开更多
Inflammatory bowel disease(IBD)has as a main characteristic the exacerbation of the immune system against enterocytes,compromising the individual’s intestinal microbiota.This inflammatory cascade causes several nutri...Inflammatory bowel disease(IBD)has as a main characteristic the exacerbation of the immune system against enterocytes,compromising the individual’s intestinal microbiota.This inflammatory cascade causes several nutritional deficiencies,which further compromise immunological functioning and,as a result,worsen the prognosis.This vicious cycle can be interrupted as the patient’s dietary pattern meets their needs according to their clinical condition,acting directly on the inflammatory process of IBD through the interaction of food,intestinal microbiota,and epigenome.Specific nutritional intervention for IBD has a crucial role in preventing and managing disease activity.This review addresses epigenetic modifications through dietary compounds as a mechanism for modulating the intestinal microbiota of patients with IBD.展开更多
Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy h...Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy has a limited impact on cure rates and long-term survival.Novel and/or improved CRC therapeutic options are needed.The involvement of microRNAs(miRNAs)in cancer development has been reported,and their regulation in many oncogenic pathways suggests their potent tumor suppressor action.Although miRNAs provide a promising therapeutic approach for cancer,challenges such as biodegradation,specificity,stability and toxicity,impede their progression into clinical trials.Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy.The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.展开更多
The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa c...The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries.These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries.In addition,it is possible to increase the content of neurotrophic factors,at the site of injury,exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy.The advantages of olfactory mucosa cells,in combination with neurotrophic factors,open up wide possibilities for their application in threedimensional and four-dimensional bioprinting technology treating spinal cord injuries.展开更多
The aim of the present study was to screen cardioactive herbs from Western Ghats of India.The heart beat rate (HBR) and blood flow during systole and diastole were tested in zebrafish embryos.We found that Cynodon dac...The aim of the present study was to screen cardioactive herbs from Western Ghats of India.The heart beat rate (HBR) and blood flow during systole and diastole were tested in zebrafish embryos.We found that Cynodon dactylon (C.dactylon) induced increases in the HBR in zebrafish embryos with a HBR of (3.968±0.344) beats/s,which was significantly higher than that caused by betamethosone [(3.770±0.344) beats/s].The EC 50 value of C.dactylon was 3.738 μg/mL.The methanolic extract of Sida acuta (S.acuta) led to decreases in the HBR in zebrafish embryos [(1.877±0.079) beats/s],which was greater than that caused by nebivolol (positive control).The EC 50 value of Sida acuta was 1.195 μg/mL.The untreated embryos had a HBR of (2.685±0.160) beats/s at 3 d post fertilization (dpf).The velocities of blood flow during the cardiac cycle were (2,291.667±72.169) μm/s for the control,(4,250±125.000) μm/s for C.dactylon and (1,083.333±72.169) μm/s for S.acuta.The LC 50 values were 32.6 μg/mL for C.dactylon and 20.9 μg/mL for S.acuta.In addition,the extracts exhibited no chemical genetic effects in the drug dosage range tested.In conclusion,we developed an assay that can measure changes in cardiac function in response to herbal small molecules and determine the cardiogenic effects by microvideography.展开更多
Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the co...Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.展开更多
Objective:The aim of the present study was to isolate the anti-MRSA(Methicillin Resistant Staphylococcus aureus)molecule from the Mangrove symbiont Streptomyces and its biomedical studies in Zebrafish embryos.Methods:...Objective:The aim of the present study was to isolate the anti-MRSA(Methicillin Resistant Staphylococcus aureus)molecule from the Mangrove symbiont Streptomyces and its biomedical studies in Zebrafish embryos.Methods:MRSA was isolated from the pus samples of Colachal hospitals and confirmed by amplification of mecA gene.Anti-MRSA molecule producing strain was identified by!6s rRNA gene sequencing.Anti-MRSA compound production was optimized by Solid State Fermentation(SSF)and the purification of the active molecule was carried out by TLC and RP-HPLC.The inhibitory concentration and LC_(50)were calculated using Statistical software SPSS.The Biomedical studies including the cardiac assay and organ toxicity assessment were carried out in Zebraiish.Results:The bioactive anti-MRSA small molecule A,was purified by TLC with Rf value of 0.37 with 1.389 retention time at RP-HPLC.The Inhibitory Concentration of the purified molecule A_2 was 30μg/mL but,the inhibitory concentration of the MRSA in the infected embryo was 32-34μg/mL for TLC purified molecule A,with LC_(50)mean value was61.504μg/mL.Zebrafish toxicity was assessed in 48-60μg/mL by observing the physiological deformities and the heart beat rates(HBR)of embryos for anti MRSA molecule showed the mean of 41.33-41.67 HBR/15 seconds for 40μg/mL and control was 42.33-42.67 for 15 seconds which significantly showed that the anti-MRSA molecule A_2 did not affected the HBR.Conclusions:Anti-MRSA molecule from Streptomyces sp PVRK-I was isolated and biomedical studies in Zebrafish model assessed that the molecule was non toxic at the minimal inhibitory concentration of MRSA.展开更多
AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when...AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq(740 MBq/m L) ^(131)I-anti EGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of ^(131)I-anti EGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of ^(131)I-antiEGFR-BSA-PCL and ^(131)I-BSA-PCL reached maximum levels at 4 h after incubation, and the ^(131)I uptake of ^(131)I-anti EGFR-BSA-PCL was higher than that of ^(131)I-BSAPCL in vitro. The ^(131)I tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g(%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL. The volume of tumor increased, and treatment rate with ^(131)I-anti EGFR-BSA-PCL was 124% ± 7%, lower than that with ^(131)I-BSA-PCL(127% ± 9%), ^(131)I(143% ± 7%), and normal saline(146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with ^(131)I-anti EGFR-BSA-PCL. The animals injected with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of ^(131)I-anti EGFR-BSA-PCL for treating colorectal cancer. ^(131)I-anti EGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.展开更多
The present study evaluated submergence responses in 88 lowland indigenous rice(Oryza sativa L.) landraces from Koraput, India, to identify submergence-tolerant rice genotypes. In pot experiments, variations in surviv...The present study evaluated submergence responses in 88 lowland indigenous rice(Oryza sativa L.) landraces from Koraput, India, to identify submergence-tolerant rice genotypes. In pot experiments, variations in survival rate, shoot elongation, relative growth index, dry matter, chlorophyll, soluble sugar and starch contents were evaluated in two consecutive years under well-drained and completely submerged conditions. Principal component analysis showed that the first three axes contributed 96.820% of the total variation among the landraces, indicating wide variation between genotypes. Major traits such as survival rate, relative growth index, soluble sugar and starch contents appeared to be important determinants of phenotypic diversity among the landraces. Phenotypic coefficient of variance was higher than genotypic coefficient of variance for all the traits and all showed high heritability(90.38%–99.54%). Five rice landraces(Samudrabali, Basnamundi, Gadaba, Surudaka and Dokarakuji) were the most tolerant to submergence. When submerged for up to 14d, Samudrabali, Basnamundi and Godoba were notable for having greater survival rates than a standard submergence tolerant variety FR13 A, and also notable for elongating more vigorously and accumulating more biomass. These three landraces may therefore be especially useful in lowland rice growing areas that are affected by both moderate stagnant water and flash flooding. Molecular genotyping revealed that the submergence tolerance of Samudrabali, Basnamundi and Godoba is linked to the presence of one or more different Sub1 loci and it may well prove useful for breeding improved submergence tolerant rice varieties, thereby assising to improve yield stability in the rainfed lowland agro-ecosystem.展开更多
AIM: To examine whether the heteroplasmy level for 15059G>A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participa...AIM: To examine whether the heteroplasmy level for 15059G>A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participants randomly selected from general population (90 males and 106 females) who underwent a regular medical check-up at the Institute for Ath-erosclerosis Research (Moscow, Russia). One hundred and twenty of them (61%) had essential hypertension, and 76 (39%) were apparently healthy normotensive persons. The level of heteroplasmy for 15059G>A mutation occurring in the coding region of cytochrome b gene (MT-CYB) of mtDNA isolated from the blood leukocytes, was quantified using DNA pyrosequencing method. RESULTS: The 15059G>A heteroplasmy level ranged between 4% and 83%, with a median level of 31%. Between the upper and lower quartiles of 15059G>A heteroplasmy distribution, significant differences were observed for patients' age, systolic blood pressure, and triglyceride levels. 15059G>A heteroplasmy correlated both with age (r = 0.331, P < 0.001) and the presence of hypertension (r = 0.228, P = 0.002). Regression analysis revealed that the age explains 12% variability of 15059G>A heteroplasmy, and hypertension independently explains more 5% variability. The 15059G>A heteroplasmy exceeding 31% was found to be significantly associated with a higher risk of essential hypertension (odds ratio 2.76; P (Fisher) 0.019]. The study participants with high 15059G>A heteroplasmy level were found to have significantly higher age (P < 0.001) and the prevalence of essential hypertension (P = 0.033), as compared to those with low 15059G>A heteroplasmy level. These observations suggested a positive correlation between the level of 15059G>A heteroplasmy and essential hypertension. CONCLUSION: This study provides the evidence of association of mtDNA 15059G>A mutation heteroplasmy with essential hypertension.展开更多
Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the ...Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.展开更多
Globally,vast research interest is emerging towards the development of biodegradable orthopedic implants as it overcomes the toxicity exerted by non-degradable implants when fixed in the human body for a longer period...Globally,vast research interest is emerging towards the development of biodegradable orthopedic implants as it overcomes the toxicity exerted by non-degradable implants when fixed in the human body for a longer period.In this context,magnesium(Mg)plays a major role in the production of biodegradable implants owing to their characteristic degradation nature under the influence of body fluids.Also,Mg is one of the essential nutrients required to perform various metabolic activities by the human cells,and therefore,the degraded Mg products will be readily absorbed by the nearby tissues.Nevertheless,the higher corrosion rate in the biological environment is the primary downside of using Mg implants that liberate H2gas resulting in the formation of cavities.Further,in certain cases,Mg undergoes complete degradation before the healing of damaged bone tissue and cannot serve the purpose of providing mechanical support.So,many studies have been focused on the development of different strategies to improve the corrosion-resistant behavior of Mg according to the requirement.In this regard,the present review focused on the limitations of using pure Mg and Mg alloys for the fabrication of medical implants and how the calcium phosphate conversion coating alters the corrosive tendency through the formation of hydroxyapatite protective films for enhanced performance in medical implant applications.展开更多
Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses, even against pebrine as well. Methods: Petri dishes...Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses, even against pebrine as well. Methods: Petri dishes and transmission electronic microscope were applied to observe silver nanoparticles against bacteria strains and nuclear polyhedral viruses (NPV) and cytoplasmic polyhedral viruses (CPV). For biological test, 108 CFU/mL NPV with strong pathogenicity, and the NPV samples treated with 1:100 ratio of “Sumerian Silver” for 8 hrs were sprayed on the mulberry leaves, respectively, for silkworm rearing. Conclusion: Silver nanoparticle solution showed a strong bactericidal effect against both G+ and G﹣bacterial pathogenic strains from Bombyx mori and mulberry. Under transmission electronic microscope (TEM), Bacillus sp. Samples showed light particles in the cells when treated with silver nanoparticles, in contrast, untreated samples showed homogeneity contents. Further, NPV particles showed no significant differences between treated and untreated samples, but CPV showed strong effects that almost all CPV were collapsed. For biological test, “Sumerian Silver” treated NPV showed no diseased silkworm but nearly all silkworms were dead with no treatment. It seems like that silver nanoparticles were proved to be more effective against CPV than that of NPV. The significant differences between two antivirus or virucidal mechanism should be greatly aroused the scientific interest.展开更多
A novel coronavirus of zoonotic origin(SARSCoV-2)has recently been recognized in patients with acute respiratory disease.COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coron...A novel coronavirus of zoonotic origin(SARSCoV-2)has recently been recognized in patients with acute respiratory disease.COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses.The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses.Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients.However,these techniques are expensive and not readily available for point-of-care(POC)applications.Currently,lack of any rapid,available,and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem.To solve the negative features of clinical investigation,we provide a brief introduction of the general features of coronaviruses and describe various amplification assays,sensing,biosensing,immunosensing,and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2.All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus,i.e.,SARS-CoV-2.Also,the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading.Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases,LAMP-based methods and LFAs are of great importance for their numerous benefits,which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.展开更多
Balancing the risks and benefits of organophosphate pesticides(OPs)on human and environmental health relies partly on their accurate measurement.A highly sensitive fluorescence anti-quenching multi-residue bio-barcode...Balancing the risks and benefits of organophosphate pesticides(OPs)on human and environmental health relies partly on their accurate measurement.A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs(triazophos,parathion,and chlorpyrifos)in apples,turnips,cabbages,and rice.Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs.DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification.The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore.The resulting fluorescence signal enables multiplexed quantification of triazophos,parathion,and chlorpyrifos residues over the concentration range of 0.01-25,0.01-50,and 0.1-50 ng/mL with limits of detection of 0.014,0.011,and 0.126 ng/mL,respectively.The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%-17.6%,which correlate well with results obtained by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The proposed bio-barcode immunoassay is stable,reproducible and reliable,and is able to detect low residual levels of multi-residue OPs in agricultural products.展开更多
BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cell...BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.展开更多
This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan (O-CMC) as a drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a ...This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan (O-CMC) as a drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein and transferrin to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-Tat-Tf as a drug carrier, Methotrexate (MTX) was incorporated as a model drug and MTX-loaded O-MNPs-Tat-Tf with an average diameter of 75 nm were prepared and characterized by TEM, AFM and VSM.The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 cells. The results showed that the MTX-loaded O-MNPs-Tat-Tf retained significant antitumor toxicity.展开更多
Cancer has become the leading cause of death.The progress in diagnosis and treatment is still limited.Over the past three decades,emergence and rapid development of nanotechnology have brought new hopes for cancer the...Cancer has become the leading cause of death.The progress in diagnosis and treatment is still limited.Over the past three decades,emergence and rapid development of nanotechnology have brought new hopes for cancer therapy.A repertoire of nanomaterials with controllable size-,shape-,and composition-dependent physiochemical proper展开更多
基金supported by The Plastic Surgery Foundation Research Pilot Grant,No.627383(to KAS).
文摘Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.
文摘Inflammatory bowel disease(IBD)has as a main characteristic the exacerbation of the immune system against enterocytes,compromising the individual’s intestinal microbiota.This inflammatory cascade causes several nutritional deficiencies,which further compromise immunological functioning and,as a result,worsen the prognosis.This vicious cycle can be interrupted as the patient’s dietary pattern meets their needs according to their clinical condition,acting directly on the inflammatory process of IBD through the interaction of food,intestinal microbiota,and epigenome.Specific nutritional intervention for IBD has a crucial role in preventing and managing disease activity.This review addresses epigenetic modifications through dietary compounds as a mechanism for modulating the intestinal microbiota of patients with IBD.
基金funded by the Department of Science and Innovation/Mintek Nanotechnology Innovation Centre.
文摘Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy has a limited impact on cure rates and long-term survival.Novel and/or improved CRC therapeutic options are needed.The involvement of microRNAs(miRNAs)in cancer development has been reported,and their regulation in many oncogenic pathways suggests their potent tumor suppressor action.Although miRNAs provide a promising therapeutic approach for cancer,challenges such as biodegradation,specificity,stability and toxicity,impede their progression into clinical trials.Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy.The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.
文摘The review focuses on the most important areas of cell therapy for spinal cord injuries.Olfactory mucosa cells are promising for transplantation.Obtaining these cells is safe for patients.The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries.These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries.In addition,it is possible to increase the content of neurotrophic factors,at the site of injury,exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy.The advantages of olfactory mucosa cells,in combination with neurotrophic factors,open up wide possibilities for their application in threedimensional and four-dimensional bioprinting technology treating spinal cord injuries.
文摘The aim of the present study was to screen cardioactive herbs from Western Ghats of India.The heart beat rate (HBR) and blood flow during systole and diastole were tested in zebrafish embryos.We found that Cynodon dactylon (C.dactylon) induced increases in the HBR in zebrafish embryos with a HBR of (3.968±0.344) beats/s,which was significantly higher than that caused by betamethosone [(3.770±0.344) beats/s].The EC 50 value of C.dactylon was 3.738 μg/mL.The methanolic extract of Sida acuta (S.acuta) led to decreases in the HBR in zebrafish embryos [(1.877±0.079) beats/s],which was greater than that caused by nebivolol (positive control).The EC 50 value of Sida acuta was 1.195 μg/mL.The untreated embryos had a HBR of (2.685±0.160) beats/s at 3 d post fertilization (dpf).The velocities of blood flow during the cardiac cycle were (2,291.667±72.169) μm/s for the control,(4,250±125.000) μm/s for C.dactylon and (1,083.333±72.169) μm/s for S.acuta.The LC 50 values were 32.6 μg/mL for C.dactylon and 20.9 μg/mL for S.acuta.In addition,the extracts exhibited no chemical genetic effects in the drug dosage range tested.In conclusion,we developed an assay that can measure changes in cardiac function in response to herbal small molecules and determine the cardiogenic effects by microvideography.
基金Supported by The Russian Ministry of Science and Education
文摘Mitochondrial DNA(mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system.This explains an increased mutation rate of mtDNA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion.In diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.
基金Supported by Xpression Biotek Ltd.and International Centre for Nanobiotechnology(ICN).Manonmaniam Sundaranar University
文摘Objective:The aim of the present study was to isolate the anti-MRSA(Methicillin Resistant Staphylococcus aureus)molecule from the Mangrove symbiont Streptomyces and its biomedical studies in Zebrafish embryos.Methods:MRSA was isolated from the pus samples of Colachal hospitals and confirmed by amplification of mecA gene.Anti-MRSA molecule producing strain was identified by!6s rRNA gene sequencing.Anti-MRSA compound production was optimized by Solid State Fermentation(SSF)and the purification of the active molecule was carried out by TLC and RP-HPLC.The inhibitory concentration and LC_(50)were calculated using Statistical software SPSS.The Biomedical studies including the cardiac assay and organ toxicity assessment were carried out in Zebraiish.Results:The bioactive anti-MRSA small molecule A,was purified by TLC with Rf value of 0.37 with 1.389 retention time at RP-HPLC.The Inhibitory Concentration of the purified molecule A_2 was 30μg/mL but,the inhibitory concentration of the MRSA in the infected embryo was 32-34μg/mL for TLC purified molecule A,with LC_(50)mean value was61.504μg/mL.Zebrafish toxicity was assessed in 48-60μg/mL by observing the physiological deformities and the heart beat rates(HBR)of embryos for anti MRSA molecule showed the mean of 41.33-41.67 HBR/15 seconds for 40μg/mL and control was 42.33-42.67 for 15 seconds which significantly showed that the anti-MRSA molecule A_2 did not affected the HBR.Conclusions:Anti-MRSA molecule from Streptomyces sp PVRK-I was isolated and biomedical studies in Zebrafish model assessed that the molecule was non toxic at the minimal inhibitory concentration of MRSA.
基金Supported by the National Natural Science Foundation of China,No.81301244(to Li W)the National Key Clinical Specialty Project
文摘AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq(740 MBq/m L) ^(131)I-anti EGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of ^(131)I-anti EGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of ^(131)I-antiEGFR-BSA-PCL and ^(131)I-BSA-PCL reached maximum levels at 4 h after incubation, and the ^(131)I uptake of ^(131)I-anti EGFR-BSA-PCL was higher than that of ^(131)I-BSAPCL in vitro. The ^(131)I tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g(%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL. The volume of tumor increased, and treatment rate with ^(131)I-anti EGFR-BSA-PCL was 124% ± 7%, lower than that with ^(131)I-BSA-PCL(127% ± 9%), ^(131)I(143% ± 7%), and normal saline(146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with ^(131)I-anti EGFR-BSA-PCL. The animals injected with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of ^(131)I-anti EGFR-BSA-PCL for treating colorectal cancer. ^(131)I-anti EGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.
文摘The present study evaluated submergence responses in 88 lowland indigenous rice(Oryza sativa L.) landraces from Koraput, India, to identify submergence-tolerant rice genotypes. In pot experiments, variations in survival rate, shoot elongation, relative growth index, dry matter, chlorophyll, soluble sugar and starch contents were evaluated in two consecutive years under well-drained and completely submerged conditions. Principal component analysis showed that the first three axes contributed 96.820% of the total variation among the landraces, indicating wide variation between genotypes. Major traits such as survival rate, relative growth index, soluble sugar and starch contents appeared to be important determinants of phenotypic diversity among the landraces. Phenotypic coefficient of variance was higher than genotypic coefficient of variance for all the traits and all showed high heritability(90.38%–99.54%). Five rice landraces(Samudrabali, Basnamundi, Gadaba, Surudaka and Dokarakuji) were the most tolerant to submergence. When submerged for up to 14d, Samudrabali, Basnamundi and Godoba were notable for having greater survival rates than a standard submergence tolerant variety FR13 A, and also notable for elongating more vigorously and accumulating more biomass. These three landraces may therefore be especially useful in lowland rice growing areas that are affected by both moderate stagnant water and flash flooding. Molecular genotyping revealed that the submergence tolerance of Samudrabali, Basnamundi and Godoba is linked to the presence of one or more different Sub1 loci and it may well prove useful for breeding improved submergence tolerant rice varieties, thereby assising to improve yield stability in the rainfed lowland agro-ecosystem.
基金Supported by The Russian Ministry of Science and Education
文摘AIM: To examine whether the heteroplasmy level for 15059G>A mutation in the mitochondrial genome might be associated with essential hypertension. METHODS: This cross-sectional study involved 196 unrelated participants randomly selected from general population (90 males and 106 females) who underwent a regular medical check-up at the Institute for Ath-erosclerosis Research (Moscow, Russia). One hundred and twenty of them (61%) had essential hypertension, and 76 (39%) were apparently healthy normotensive persons. The level of heteroplasmy for 15059G>A mutation occurring in the coding region of cytochrome b gene (MT-CYB) of mtDNA isolated from the blood leukocytes, was quantified using DNA pyrosequencing method. RESULTS: The 15059G>A heteroplasmy level ranged between 4% and 83%, with a median level of 31%. Between the upper and lower quartiles of 15059G>A heteroplasmy distribution, significant differences were observed for patients' age, systolic blood pressure, and triglyceride levels. 15059G>A heteroplasmy correlated both with age (r = 0.331, P < 0.001) and the presence of hypertension (r = 0.228, P = 0.002). Regression analysis revealed that the age explains 12% variability of 15059G>A heteroplasmy, and hypertension independently explains more 5% variability. The 15059G>A heteroplasmy exceeding 31% was found to be significantly associated with a higher risk of essential hypertension (odds ratio 2.76; P (Fisher) 0.019]. The study participants with high 15059G>A heteroplasmy level were found to have significantly higher age (P < 0.001) and the prevalence of essential hypertension (P = 0.033), as compared to those with low 15059G>A heteroplasmy level. These observations suggested a positive correlation between the level of 15059G>A heteroplasmy and essential hypertension. CONCLUSION: This study provides the evidence of association of mtDNA 15059G>A mutation heteroplasmy with essential hypertension.
基金the work from the European Research Council under the European Union's Seventh Framework Program(FP/2007-2013)/ERC grant agreement No.310034the Austrian Science Fund(FWF)grant No.I 3064.
文摘Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.
文摘Globally,vast research interest is emerging towards the development of biodegradable orthopedic implants as it overcomes the toxicity exerted by non-degradable implants when fixed in the human body for a longer period.In this context,magnesium(Mg)plays a major role in the production of biodegradable implants owing to their characteristic degradation nature under the influence of body fluids.Also,Mg is one of the essential nutrients required to perform various metabolic activities by the human cells,and therefore,the degraded Mg products will be readily absorbed by the nearby tissues.Nevertheless,the higher corrosion rate in the biological environment is the primary downside of using Mg implants that liberate H2gas resulting in the formation of cavities.Further,in certain cases,Mg undergoes complete degradation before the healing of damaged bone tissue and cannot serve the purpose of providing mechanical support.So,many studies have been focused on the development of different strategies to improve the corrosion-resistant behavior of Mg according to the requirement.In this regard,the present review focused on the limitations of using pure Mg and Mg alloys for the fabrication of medical implants and how the calcium phosphate conversion coating alters the corrosive tendency through the formation of hydroxyapatite protective films for enhanced performance in medical implant applications.
文摘Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses, even against pebrine as well. Methods: Petri dishes and transmission electronic microscope were applied to observe silver nanoparticles against bacteria strains and nuclear polyhedral viruses (NPV) and cytoplasmic polyhedral viruses (CPV). For biological test, 108 CFU/mL NPV with strong pathogenicity, and the NPV samples treated with 1:100 ratio of “Sumerian Silver” for 8 hrs were sprayed on the mulberry leaves, respectively, for silkworm rearing. Conclusion: Silver nanoparticle solution showed a strong bactericidal effect against both G+ and G﹣bacterial pathogenic strains from Bombyx mori and mulberry. Under transmission electronic microscope (TEM), Bacillus sp. Samples showed light particles in the cells when treated with silver nanoparticles, in contrast, untreated samples showed homogeneity contents. Further, NPV particles showed no significant differences between treated and untreated samples, but CPV showed strong effects that almost all CPV were collapsed. For biological test, “Sumerian Silver” treated NPV showed no diseased silkworm but nearly all silkworms were dead with no treatment. It seems like that silver nanoparticles were proved to be more effective against CPV than that of NPV. The significant differences between two antivirus or virucidal mechanism should be greatly aroused the scientific interest.
基金Nanjing Forestry University[Grant Nos.163020139,164020818,163020217 and 16302023]National Natural Science Foundation of China(5201101466).
文摘A novel coronavirus of zoonotic origin(SARSCoV-2)has recently been recognized in patients with acute respiratory disease.COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses.The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses.Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients.However,these techniques are expensive and not readily available for point-of-care(POC)applications.Currently,lack of any rapid,available,and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem.To solve the negative features of clinical investigation,we provide a brief introduction of the general features of coronaviruses and describe various amplification assays,sensing,biosensing,immunosensing,and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2.All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus,i.e.,SARS-CoV-2.Also,the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading.Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases,LAMP-based methods and LFAs are of great importance for their numerous benefits,which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.
基金supported by the Central Public Interest Scientific Institution Basal Research Fund for the Chinese Academy of Agricultural Sciences(Grant No.:Y2021PT05)National Institute of Environmental Health Science Superfund Research Program(Grant No.:P42 ES004699)+1 种基金National Academy of Sciences(Subaward No.:2000009144)Ningbo Innovation Project for Agro-Products Quality and Safety(Grant No.:2019CXGC007).
文摘Balancing the risks and benefits of organophosphate pesticides(OPs)on human and environmental health relies partly on their accurate measurement.A highly sensitive fluorescence anti-quenching multi-residue bio-barcode immunoassay was developed to detect OPs(triazophos,parathion,and chlorpyrifos)in apples,turnips,cabbages,and rice.Gold nanoparticles were functionalized with monoclonal antibodies against the tested OPs.DNA oligonucleotides were complementarily hybridized with an RNA fluorescent label for signal amplification.The detection signals were generated by DNA-RNA hybridization and ribonuclease H dissociation of the fluorophore.The resulting fluorescence signal enables multiplexed quantification of triazophos,parathion,and chlorpyrifos residues over the concentration range of 0.01-25,0.01-50,and 0.1-50 ng/mL with limits of detection of 0.014,0.011,and 0.126 ng/mL,respectively.The mean recovery ranged between 80.3% and 110.8% with relative standard deviations of 7.3%-17.6%,which correlate well with results obtained by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The proposed bio-barcode immunoassay is stable,reproducible and reliable,and is able to detect low residual levels of multi-residue OPs in agricultural products.
基金Supported by Russian Science Foundation,No.16-15-10432。
文摘BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.
文摘This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan (O-CMC) as a drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein and transferrin to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-Tat-Tf as a drug carrier, Methotrexate (MTX) was incorporated as a model drug and MTX-loaded O-MNPs-Tat-Tf with an average diameter of 75 nm were prepared and characterized by TEM, AFM and VSM.The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 cells. The results showed that the MTX-loaded O-MNPs-Tat-Tf retained significant antitumor toxicity.
文摘Cancer has become the leading cause of death.The progress in diagnosis and treatment is still limited.Over the past three decades,emergence and rapid development of nanotechnology have brought new hopes for cancer therapy.A repertoire of nanomaterials with controllable size-,shape-,and composition-dependent physiochemical proper
