Polymeric Nanofibers for Drug Delivery Applications: A Recent Review.

With the rapid development of biomaterials and biotechnologies, various functional materials-based drug delivery systems (DDS) are developed to overcome the limitations of traditional drug release formulations, such as uncontrollable drug concentration in target organs/tissues and unavoidable adverse reactions. Polymer nanofibers exhibit promising characteristics including easy preparation, adjustable features of wettability and elasticity, tailored surface and interface properties, and surface-to-volume ratio, and are used to develop new DDS. Different kinds of drugs can be incorporated into the polymer nanofibers. Additionally, their release kinetics can be modulated via the preparation components, component proportions, and preparation processes, enabling their applications in several fields. A timely and comprehensive summary of polymeric nanofibers for DDS is thus highly needed. This review first describes the common methods for polymer nanofiber fabrication, followed by introducing controlled techniques for drug loading into and release from polymer nanofibers. Thus, the applications of polymer nanofibers in drug delivery were summarized, particularly focusing on the relation between the physiochemical properties of polymeric nanofibers and their DDS performance. It is ended by listing future perspectives. Graphical abstract.

Accuracy of ultrasound elastography for predicting breast cancer response to neoadjuvant chemotherapy: A systematic review and meta-analysis.

BACKGROUND: Several studies have reported the prognostic value of ultrasound elastography (UE) in patients receiving neoadjuvant chemotherapy (NACT) for breast cancer. However, the assessment of parameters differed between shear-wave elastography and strain elastography in terms of measured elasticity parameter and mode of imaging. It is important, therefore, to assess the accuracy of the two modes of elastography. AIM: To assess the accuracy of UE for predicting the pathologic complete response (pCR) in breast cancer patients following NACT. METHODS: A comprehensive and systematic search was performed in the databases of MEDLINE, EMBASE, SCOPUS, PubMed Central, CINAHL, Web of Science and Cochrane library from inception until December 2020. Meta-analysis was performed using STATA software "Midas" package. RESULTS: A total of 14 studies with 989 patients were included. The pooled sensitivities were 86% [95% confidence interval (CI): 76%-92%] for UE, 77% (95%CI: 68%-84%) for shear-wave elastography, and 92% (95%CI: 73%-98%) for strain-wave elastography. The pooled score specificities were 86% (95%CI: 80%-90%) for UE, 84% (95%CI: 72%-91%) for shear-wave elasticity, and 87% (95%CI: 81%-92%) for strain-wave elastography. A significant heterogeneity was found among studies based on the chi-square test results and an I 2 statistic > 75%. CONCLUSION: Strain-wave type of UE can accurately predict the pCR following NACT amongst breast cancer patients. Studies exploring its accuracy in different ethnic populations are required to strengthen the evidence.

In situ polymerization of conducting polymers around living neural cells: Cellular effect study.

Conducting polymer has been directly polymerized around living neural cells or in the cortex with the aim of creating an intimate contact between implantable electrical devices and electrogenetic cells. The long term cellular effect after conductive polymer coating, a critical issue for practical applications, has not been reported. In this study, poly(3,4-ethylenedioxythiophene) PEDOT was directly polymerized around the living primary neural and PC12 cells under varying current densities, potentials and charge-balanced current pulses. The cell morphology, nuclei evolution, and cell viability post PEDOT polymerization were studied at different time points. The aim of this study was to investigate the immediate and long-term cellular response towards in-situ polymerization of conductive polymers and to provide experimental information on the feasibility of this technique in practical applications.

Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance.

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies.

Nanostructured PEDOT Coatings for Electrode-Neuron Integration.

Neural electrodes have been developed for the diagnosis and treatment of stroke, sensory deficits, and neurological disorders based on the electrical stimulation of nerve tissue and recording of neural electrical activity. A low interface impedance and large active surface area for charge transfer and intimate contact between neurons and the electrode are critical to obtain high-quality neural signal and effective stimulation without causing damage to both tissue and electrode. In this study, a nanostructured poly(3,4-ethylenedioxythiophene) (PEDOT) coating with lots of long protrusions was created via a one-step electrochemical polymerization from a dichloromethane solution without any rigid or soft templates. The nanostructures on the PEDOT coating were basically formed by intertwined PEDOT nanofibers, which further enhanced the active surface area. The fuzzy PEDOT-modified microelectrodes exhibited an impedance as low as 1 kΩ at 1 kHz, which is much lower than those produced from aqueous 3,4-ethylenedioxythiophene (EDOT) solution, and it was comparable with PEDOT films or composites created from/with template materials. Also, more than 150 times larger charge storage capacity density was obtained compared to the unmodified microelectrode. An in vitro biocompatibility test performed on PC12 cells and primary cells suggested that the PEDOT coatings support cell adhesion, growth, and neurite extension. These results suggest the great potential of the nanostructured PEDOT coating as an electroactive and biosafe intimate contact between the implanted neural electrode and neurons.

New 30-norlupane derivatives through chemical-microbial semi-synthesis of betulinic acid and their neuroprotective effect.

In this study, seven 30-norlupane derivatives (2-8) wasobtained from the chemical oxidation ofbetulinic acidfollowed bybiotransformationviaBacillus megateriumCGMCC 1.1741. And metabolites 2-4 and 6-8 were newly identified products. In the first step, betulinic acid was chemically oxidizedto platanic acid (1). Following the chemical oxidation, B. megaterium catalyzed the hydroxylation at C-7, C-11, C-15 and C-23 of platanic acid (1) as well as the oxidation of C-3 hydroxyl group. Compared to the labor-intensive isolation from natural plants, this chemical-microbial semi-synthesis is more capable to provide increased structural diversity of oxygenated 30-norlupane. Finally, the potential neuroprotective effect of the derivatives was assessed on neuron-like PC12 cells induced by cobalt chloride (CoCl2). Metabolite 6 showed a potent neuroprotective activity.

Detection and molecular epidemiology of ferlaviruses in farmed snakes with respiratory disease in Guangxi Province, China.

We screened 104 snakes with respiratory disease, collected from 52 snake farms in Guangxi Province, China, for pathogens. Ferlaviruses were detected in 70 of 104 lung samples by reverse-transcription PCR; 34 of 52 of the snake farms were positive for ferlaviruses. No reovirus, adenovirus, sunshine virus, or nidovirus was detected in any of the snakes. We obtained 96 bacterial isolates from snake organs, of which the most commonly isolated species were Salmonella (18) and Proteus (16). Sequence analysis, based on 27 partial RNA-dependent RNA polymerase gene (L) sequences, revealed that ferlaviruses from Guangxi and the known GenBank strains clustered together and formed 3 genogroups. The nucleotide and deduced amino acid homologies of ferlaviruses were 84.3-100% and 95.0-100% within groups, respectively, and 77.0-81.6% and 90.4-95.2% between groups, respectively. Ferlaviruses from Guangxi had close genetic relationships with the known GenBank strains. Our results indicate that ferlaviruses are common in snakes with respiratory disease on the farms of Guangxi that we sampled, and that ferlavirus molecular epidemiology is both diverse and complex.

Application of tandem biotransformation for biosynthesis of new pentacyclic triterpenoid derivatives with neuroprotective effect.

Tandem whole-cell biotransformation was applied successfully to deliver novel pentacyclic triterpenoid derivatives for the first time. In this process, the starting substrate oleanolic acid (1) was biotransformed into a hydroxylated metabolite 1a by Rhizopus chinensis CICC 40335 and then was further glycosylated to 1b by Bacillus subtilis ATCC 6633. Moreover, metabolite 1a was furtherly oxidized by Streptomyces griseus ATCC 13273 and generated two new derivatives as 1c and 1d. To validate the feasibility, tandem biotransformation of 18ß-glycyrrhetinic acid (2) by R. chinensis and B. subtilis was also conducted and offered a glycosylated derivative (2c). Finally, the neuroprotective effects of the derivatives were assessed on neural injury PC12 cell model induced by cobalt chloride.

Efficacy of low-temperature plasma-activated gas disinfection against biofilm on contaminated GI endoscope channels.

BACKGROUND AND AIMS: It has been increasingly recognized that the safety of GI endoscopes needs to be improved by addressing the small margin of safety of high-level disinfectants (HLDs) and the failure of HLDs to clear multidrug-resistant organisms and biofilms. There is also an unmet need for effective low-temperature sterilization techniques that have a clear pathway for U.S. Food and Drug Administration clearance. Here, we report the results of our investigation of a novel argon plasma-activated gas (PAG) for disinfection and potentially sterilization of biofilm-contaminated endoscopic channels. METHODS: Test polytetrafluoroethylene channel segments were contaminated with 4-, 24- and 48-hour luminal biofilms of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, or Escherichia coli and were treated by PAG flowing for up to 9 minutes. After PAG treatment, inactivation and dispersal of luminal bacterial biofilms and their regrowth in 48 hours were evaluated. Reactive species induced by PAG were measured with colorimetric probes and electron spin resonance spectrometry. Surface morphology and elemental composition of PAG-treated channel material were analyzed with scanning electron microscopy. RESULTS: PAG treatment for 9 minutes led to more than 8 log reduction of viable cells and dispersal of 24- and 48-hour luminal biofilms of all 3 bacteria and to suppression of their regrowth, whereas it resulted in little morphologic abnormalities in channel material. Ozone concentration of PAG fell to below .01 ppm within 30 seconds of switching off the plasma. PAG-treated deionized water was acidified with numerous types of reactive species, each with a concentration some 3 orders of magnitude or more below its bacterial inhibition concentration. CONCLUSIONS: PAG is capable of effectively and rapidly disinfecting luminal bacterial biofilms and offers an alternative to the step of HLDs and/or ethylene oxide in the endoscope reprocessing procedure with safety to personnel and environment.

Sargassum polysaccharide inhibits inflammatory response in PCV2 infected-RAW264.7 cells by regulating histone acetylation.

Toxic inflammatory response is frequently introduced upon virus infection. In this study, RAW264.7 cells were infected with porcine circovirus type 2 (PCV2) and treated with Sargassum polysaccharide SP. It was found that PCV2 infection induced increased significant inflammation response represented with increased secretion of inflammatory cytokines, corresponding with promoted HAT activity, inhibited HDAC activity, elevated HDAC1 mRNA levels, and up-regulated acetylation levels of H3 and H4 in RAW264.7 cells. SP treatment significantly inhibited the increase of inflammatory cytokines, HAT activity and the acetylation of histones, but dramatically increased the HDAC activity and the expression of HDAC1. From these results, SP might be able to protect immune cells from virus induced damages through inhibiting the inflammatory responds by maintaining an equilibrium between the activity of HATs and HDACs which contributes to an appropriate level of histone acetylation.

Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution.

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 min led to regrowth of bacteria and fungi, up to 107 to 109 CFU/ml, in 24 h. The PAD lock solution had minimal impact on human umbilical vein endothelial cell viability, whereas the minocycline-EDTA-ethanol solution elicited cell death in nearly half of human endothelial cells. Additionally, PAD treatment caused little topological change to catheter materials. In conclusion, PAD represents a novel antibiotic-free, noncytotoxic lock solution that elicits rapid and broad-spectrum eradication of biofilm-laden microbes and shows promise for the prevention and treatment of intravascular catheter infections.

Immunomodulatory and antioxidant effects of total flavonoids of Spatholobus suberectus Dunn on PCV2 infected mice.

Oxidative stress plays an important role in the pathogenesis of virus infection and antioxidants are becoming promising candidates as therapeutic agents. This study is designed to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on oxidative stress in mice induced by porcine circovirus type 2 (PCV2) infection. The PCV2 infection leads to significant decrease in thymus and spleen indices, elevation of xanthine oxidase (XOD) and myeloperoxidase (MPO) activities, reduction in GSH level and GSH to GSSG ratio and decline of superoxide dismutase (SOD) activity, indicating the formation of immunosuppression and oxidative stress. TFSD treatment recovered the alteration of viscera index, antioxidant content and activities of oxidative-associated enzymes to a level similar to control. Our findings suggested that PCV2 induced immunosuppression and oxidative stress in mice and TFSD might be able to protect animals from virus infection via regulation of immune function and inhibition of oxidative stress.

Effect of total flavonoids of Spatholobus suberectus Dunn on PCV2 induced oxidative stress in RAW264.7 cells.

BACKGROUND: This study was carried out to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on PCV2 induced oxidative stress in RAW264.7 cells. METHODS: Oxidative stress model was established in RAW264.7 cells by infecting with PCV2. Virus infected cells were then treated with various concentrations (25 mg/ml, 50 mg/ml and 100 mg/ml) of TFSD. The levels of oxidative stress related molecules (NO, ROS, GSH and GSSG) and activities of associated enzymes (SOD, MPO and XOD were analyzed using ultraviolet spectrophotometry, fluorescence method and commercialized detection kits. RESULTS: PCV2 infection induced significant increase of NO secretion, ROS generation, GSSG content, activities of both XOD and MPO, and dramatically decrease of GSH content and SOD activity in RAW264.7 cells (P < 0.05). After treating with TFSD, PCV2 induced alteration of oxidative stress related molecule levels and enzyme activities were recovered to a level similar to control. CONCLUSION: Our findings indicated that TFSD was able to regulate oxidative stress induced by PCV2 infection in RAW264.7 cells, which supports the ethnomedicinal use of this herb as an alternative or complementary therapeutic drug for reactive oxygen-associated pathologies.

Conductive artificial biofilm dramatically enhances bioelectricity production in Shewanella-inoculated microbial fuel cells.

A new strategy of electrogen immobilization was developed to construct a conductive artificial biofilm (CAB) on an anode of a microbial fuel cell (MFC). The MFCs equipped with an optimized CAB exhibited an eleven fold increase in power output compared with natural biofilms.

The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development.

Mutations in the gene encoding FERM domain-containing 7 protein (FRMD7) are recognized as an important cause of X-linked idiopathic infantile nystagmus (IIN). However, the precise role of FRMD7 and its involvement in the pathogenesis of IIN are not understood. In the present study, we have explored the role of FRMD7 in neuronal development. Using in situ hybridization and immunohistochemistry, we reveal that FRMD7 expression is spatially and temporally regulated in both the human and mouse brain during embryonic and fetal development. Furthermore, we show that FRMD7 expression is up-regulated upon retinoic acid (RA)-induced differentiation of mouse neuroblastoma NEURO2A cells, suggesting FRMD7 may play a role in this process. Indeed, we demonstrate, for the first time, that knockdown of FRMD7 during neuronal differentiation results in altered neurite development. Taken together, our data suggest that FRMD7 is involved in multiple aspects of neuronal development, and have direct importance to further understanding the pathogenesis of IIN.

[Study on the association between transforming growth factor alpha gene TaqI variant and cleft lip with or without cleft palate].

OBJECTIVE: To study the association between transforming growth factor alpha gene (TGFalpha) TaqI variant and nonsyndromic cleft lip with or without cleft palate (nsCL/P) in Chinese population. METHODS: TGFalpha TaqI variant was detected using polymerase chain reaction-restriction fragment length polymorphism for DNA samples of the 149 triads with nsCL/P affected child. We performed the Transmission/disequilibrium test and the family-based association study (FBAT) to identify the associations between this variant and risk of nsCL/P. RESULTS: Significant distortion of C2 allele at TGFalpha TaqI locus in nsCL/P groups (P > 0.05) was not found. In the family-based association test, C2 allele and offspring C2C1 genotype was not found to be significantly associated with an increase risk of nsCL/P (P > 0.05). CONCLUSION: Our findings did not suggest an association between offspring TGFalpha TaqI variant and the increased risk of nsCL/P in Chinese population.

[Association between parental transforming growth factor alpha gene TaqI variant, paternal smoking and the cleft lip with or without cleft palate].

OBJECTIVE: To study the association between transforming growth factor alpha gene (TGFalpha) TaqI variant and nonsyndromic cleft lip with or without cleft palate (nsCL/P) in Chinese population, and the interaction with parental smoking. METHODS: TGFalpha TaqI variant was detected using RFLP-PCR for DNA samples of the 170 triads with nsCL/P affected child. We performed the transmission/disequilibrium test (TDT) and the family-based association study (FBAT) to test the associations between this variant and risk of nsCL/P. RESULTS: It was not found significant distortion of C2 allele at TGFalpha TaqI locus in nsCL/P groups (P > 0.05), however, by stratified analysis, we found that the rate of C2 allele transmission among nuclear families whose fathers were smoking was 1/5 (0.062 - 0.711) as compared with that among nuclear families whose fathers were not smoking, and the OR of interaction between TGFalpha variant and parental smoking is 0.102 (0.017 - 0.619). CONCLUSION: The parental smoking may interact with TGFalpha variants of Chinese populations in occurrence of nsCL/P, but it remains to have more investigations.

[Study on the association between reduced folate carrier gene polymorphism and congenital heart defects and cleft lip with or without cleft palate].

OBJECTIVE: To study the association between reduced folate carrier gene (RFC1) polymorphism and congenital heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP. METHODS: RFC1 (A80G) genotype was detected using RFLP-PCR for blood DNA of the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional supplementation of folic acid. RESULTS: Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did (OR = 2.68, 95% CI: 1.14 - 6.41). There was a statistical association between the risk of CHD and maternal periconceptional folic acid supplementation (chi(2) = 6.213, P < 0.05). In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2.140, P < 0.05) while G allele of RFC1 (A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid. CONCLUSION: Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offspring with GG, GA genotype and maternal periconceptional folicacid deficiency.

[The epidemiology of neural tube defects in high-prevalence and low-prevalence areas of China].

OBJECTIVE: To describe the epidemiology of neural tube defects (NTDs) in high- and low-prevalence areas of China. METHODS: Birth defects surveillance data, collected from 1992 through 1994 was analyzed. These data were collected as part of the Sino-American cooperative project on NTDs prevention. We classified NTDs as anencephaly, encephalocele, high-level and low-level spina bifida (SB) according to location of the lesion (high vs low) and whether the defect was isolated or occurred in association with other birth defects. Rates were compared in the high-prevalence (North) region and the low-prevalence (South) region, after adjusted for classification, urban and rural, season and sex, and calculated the adjusted rate of NTDs. RESULTS: Among seven hundred and eighty-four NTDs cases in 326 874 recorded births (include in livebirth, stillbirth and fetal death with a gestational age of at least 20 weeks), the overall NTDs prevalence in the North was 5.57/1,000 births, and in the South was 0.88/1 000. There were also significant differences in the prevalence of anencephaly, encephalocele, high-level and low-level SB between North (0.97, 0.49, 2.75 and 1.11/1,000 birth) and South (0.36, 0.15, 0.21 and 0.14/1,000 birth) (P < 0.01), with adjusted prevalences in the North 3 - 7 times higher than those in the South. There were significant difference between urban (2.04) and rural areas (6.57/1,000 birth) in the North (P < 0.01), urban (0.52) and rural areas (0.95/1,000 birth) in the South (P < 0.05). Adjusted prevalence rates in the rural were 3 - 4 times higher than those of urban in the North and 1.6 - 1.9 times higher than in the South; The seasonal rate of high-level SB increased between September and November in the North (3.44/1,000 birth), while the seasonal rate of anencephaly decreased between September and November (0.18/1,000 birth) in the South. However there were no seasonal changes in other classified NTDs both in the South and North. CONCLUSIONS: The birth prevalence of NTDs in the North of China was the highest in the world. There were significant differences between the North and the South, urban and rural. There was seasonal change in high-level SB in the North, which was in accordance to the phenotype of NTDs. It was suggested that there might exist etiological heterogeneity among anecephalus, low- and high-level SB.