Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis.

Diabetic neuropathy (DN) is the most prevalent complication of diabetes. Pharmacological treatments for DN are often limited in efficacy, so the development of new agents to alleviate DN is essential. The aim of this study was to evaluate the effects of rolipram, a selective phosphodiesterase-4 inhibitor (PDE-4I), and pentoxifylline, a general PDE inhibitor, using a rat model of DN. In this study, a diabetic rat model was established by i.p. injection of STZ (55 mg/kg). Rats were treated with rolipram (1 mg/kg), pentoxifylline (100 mg/kg), and combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for 5 weeks. After treatments, sensory function was assessed by hot plate test. Then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP, adenosine diphosphate and mitochondrial membrane potential (MMP) levels, Cytochrome c release, Bax, Bcl-2, caspase-3 proteins expression in DRG neurons were assessed by biochemical and ELISA methods, and western blot analysis. DRG neurons were histologically examined using hematoxylin and eosin (H&E) staining method. Rolipram and/or pentoxifylline significantly attenuated sensory dysfunction by modulating nociceptive threshold. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, prevented mitochondrial dysfunction, apoptosis and degeneration of DRG neurons, which appears to be mediated by inducing ATP and MMP, improving cytochrome c release, as well as regulating the expression of Bax, Bcl-2, and caspase-3 proteins, and improving morphological abnormalities of DRG neurons. We found maximum effectiveness with rolipram and pentoxifylline combination on mentioned factors. These findings encourage the use of rolipram and pentoxifylline combination as a novel experimental evidence for further clinical investigations in the treatment of DN.

Thyroid function and opium use disorder: a cross-sectional study on the Fasa adults cohort study (FACS), 2017.

BACKGROUND: Addiction increases the risk of different lifelong disorders. However, there are limited studies evaluating the effects of opioid use disorder (OUD) on thyroid function. The present study aimed to compare the thyroid function of individuals with and without OUD. METHODS: This cross-sectional study was conducted on 700 eligible participants of the Persian Cohort of Fasa, Iran. Pregnant women and participants with false or missing data were excluded from the study. Remained participants were divided into case and control groups based on the recorded history of OUD. Frozen plasma samples of the cohort bank were used to determine the levels of T3, T4, and thyroid-stimulating hormone (TSH). The thyroid function was compared between the two groups using the Mann-Whitney test (P < 0.05). RESULTS: The mean age of the final studied population (n = 648) was 54.0 ± 9.8 years, including 336 men (49.1%) and 197 participants with OUD (28.8%). The median levels of TSH, T4, and T3 were 2.91 ± 4.61, 9.26 ± 3.65, and 1.22 ± 0.49, respectively. The case group had significantly higher TSH (3.72 ± 6.2 vs. 2.58 ± 3.75, P < 0.001) and lower T4 (8 ± 3.6 vs. 9.8 ± 3.5, P < 0.001). Also, T3 was slightly lower in the case group (1.1 ± 0.5 vs. 1.3 ± 0.5; P = 0.369), although this association was only significant in female opium users (P < 0.001). CONCLUSIONS: The present findings revealed that OUD caused a reduction in T4 while increasing TSH. Therefore, OUD may lead to the development of primary hypothyroidism, which needs to be investigated in future studies.

Effective blocking of neuropilin-1activity using oligoclonal nanobodies targeting different epitopes.

Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor and when overexpressed, leads to angiogenesis. High expression of NRP-1 has been observed in various cancers. Unique characteristic of nanobodies (small size, high affinity and stability, and ease production) make them potential therapeutic tools. Oligoclonal nanobodies which detect multiple functional epitopes on the target antigen could be potential tools for inhibition of cancer resistance problems due to escape variant of tumor cells. In this study, oligoclonal anti-NRP-1 nanobodies were selected from camel immune library and their binding activities as well as in vitro functionality were evaluated. Anti-NRP-1 nanobodies were expressed in an Escherichia coli host, and purified using nickel affinity chromatography. The effect of each individual and oligoclonal nanobodies on human endothelial cells were evaluated by MTT, Tube formation, and migration assay as well. Results showed that oligoclonal anti-NRP-1 nanobodies detected different epitopes of NRP-1 antigen and inhibited in vitro angiogenesis of human endothelial cells better than each individual nanobody. Results indicate promising oligoclonal anti-NRP-1 nanobodies for inhibition of angiogenesis.

A data-informed system to manage scarce blood product allocation in a randomized controlled trial of convalescent plasma.

BACKGROUND: Equitable allocation of scarce blood products needed for a randomized controlled trial (RCT) is a complex decision-making process within the blood supply chain. Strategies to improve resource allocation in this setting are lacking. METHODS: We designed a custom-made, computerized system to manage the inventory and allocation of COVID-19 convalescent plasma (CCP) in a multi-site RCT, CONCOR-1. A hub-and-spoke distribution model enabled real-time inventory monitoring and assignment for randomization. A live CCP inventory system using REDCap was programmed for spoke sites to reserve, assign, and order CCP from hospital hubs. A data-driven mixed-integer programming model with supply and demand forecasting was developed to guide the equitable allocation of CCP at hubs across Canada (excluding Québec). RESULTS: 18/38 hospital study sites were hubs with a median of 2 spoke sites per hub. A total of 394.5 500-ml doses of CCP were distributed; 349.5 (88.6%) doses were transfused; 9.5 (2.4%) were wasted due to mechanical damage sustained to the blood bags; 35.5 (9.0%) were unused at the end of the trial. Due to supply shortages, 53/394.5 (13.4%) doses were imported from Héma-Québec to Canadian Blood Services (CBS), and 125 (31.7%) were transferred between CBS regional distribution centers to meet demand. 137/349.5 (39.2%) and 212.5 (60.8%) doses were transfused at hubs and spoke sites, respectively. The mean percentages of total unmet demand were similar across the hubs, indicating equitable allocation, using our model. CONCLUSION: Computerized tools can provide efficient and immediate solutions for equitable allocation decisions of scarce blood products in RCTs.

Physicochemical, Thermal and Rheological Properties of Pectin Extracted from Sugar Beet Pulp Using Subcritical Water Extraction Process.

The objective of this study was to characterize the properties of pectin extracted from sugar beet pulp using subcritical water (SWE) as compared to conventional extraction (CE). The research involved advanced modeling using response surface methodology and optimization of operational parameters. The optimal conditions for maximum yield of pectin for SWE and CE methods were determined by the central composite design. The optimum conditions of CE were the temperature of 90 °C, time of 240 min, pH of 1, and pectin recovery yield of 20.8%. The optimal SWE conditions were liquid-to-solid (L/S) ratio of 30% (v/w) at temperature of 130 °C for 20 min, which resulted in a comparable yield of 20.7%. The effect of obtained pectins on viscoamylograph pasting and DSC thermal parameters of corn starch was evaluated. The contents of galacturonic acid, degree of methylation, acetylation, and ferulic acid content were higher in the pectin extracted by SWE, while the molecular weight was lower. Similar chemical groups were characterized by FTIR in both SWE and CE pectins. Color attributes of both pectins were similar. Solutions of pectins at lower concentrations displayed nearly Newtonian behavior. The addition of both pectins to corn starch decreased pasting and DSC gelatinization parameters, but increased ΔH. The results offered a promising scalable approach to convert the beet waste to pectin as a value-added product using SWE with improved pectin properties.

Sugar beet pectin extracted by ultrasound or conventional heating: a comparison.

The yield and quality of sugar beet pulp pectin obtained by ultrasound-assisted extraction (UAE) were compared to those obtained by conventional heating. Extraction temperature (70-90) °C, extraction time (2-4) h and pH (1-1.5) were considered as the variables for the conventional extraction while ultrasound frequency (20-60) kHz, time (10-30) min and amplitude (60-100%) were considered as the variables for UAE. The optimal conditions for maximum yield of pectin for conventionally and ultrasonically extracted pectin were determined by the central composite design and the Box Behnken design, respectively. The optimum conditions of conventional extraction were the temperature of 90 °C, time of 4 h and pH of 1. The optimum conditions of UAE were ultrasound frequency of 20 kHz, time of 10 min, and ultrasound amplitude of 96%. Extraction using the optimized conditions of conventional heating and UAE achieved the best yield of 20.75% and 20.85%, respectively. The degree of methyl esterification, ferulic acid content and molecular weight of UAE pectin were higher than conventionally extracted pectin but the content of galacturonic acid in UAE pectin was lower than that of conventionally extracted pectin. The infrared spectra of both pectins revealed the occurrence of polysaccharide component. The pectin achieved by UAE had higher lightness value than conventionally extracted pectin, confirming its application in different products partially in bright food products. The UAE pectin possessed higher viscosity than conventionally extracted pectin. The addition of UAE pectin increased all of the DSC gelatinization parameters. Overall, UAE could be a promising scalable and economical approach to obtain pectin with unique characteristics.

Genotypic effect of a mutation of the MYBPC3 gene and two phenotypes with different patterns of inheritance.

BACKGROUND: MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM. METHODS: Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein. RESULTS AND CONCLUSION: Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.

Clinical and Radiographic Success of Electrosurgical Pulpectomy in Primary Teeth.

A pulpectomy requires the swift extraction of the inflamed tissue. Moreover, the speed of treatment is especially important in the case of uncooperative children. Conventional pulpectomies, however, often require an extended treatment period, which can therefore cause problems with such patients. Electrosurgical methods have been applied to pulpotomies for a number of years. However, to the best of our knowledge, no studies to date have assessed its application to pulpectomies. The aim of this study was to compare clinical and radiographic success rates over a 6-month follow-up period between conventional and electrosurgical pulpectomies. A total of 50 children aged 4 to 8 years were enrolled in this randomized clinical trial. A pulpectomy of the first and second primary molar teeth was seen as the optimal treatment plan in all these patients. One group was treated using the conventional method (C group, 25 teeth) and the other with electrosurgery (ES group, 25 teeth). The patients were evaluated for the presence of pain, mobility, abscess, sinus tract, erythema, tenderness to percussion, internal and external root resorption, and radiolucency. Clinical and radiographic success rates and total working time were assessed. The Fisher's exact test and Mann-Whitney U-test were used for the statistical analysis. After 6 months of follow-up, the clinical and radiographic success rates were 90.5 and 85.7%, respectively, in the ES group, compared with 88.9 and 72.2%, respectively, in the C group. No statistically significant difference was observed between the two groups (p>0.05). Working time, however, was significantly shorter in the ES group (p<0.001). This suggests that pulpectomy with electrosurgery reduces treatment time, and is therefore quite useful in situations where duration of the treatment course is of crucial concern.

Structures, Unimolecular Fragmentations, and Reactivities of the Self-Assembled Multimetallic/Peptide Complexes [Mnn (GlyGly-H)2n-1 ](+) and [Mnn+1 (GlyGly-H)2n ](2.).

Complexes of Mn(2+) with deprotonated GlyGly are investigated by sustained off-resonance irradiation collision-induced dissociation (SORI-CID), infrared multiple-photon dissociation spectroscopy, ion-molecule reactions, and computational methods. Singly [Mnn (GlyGly-H)2n-1 ](+) and doubly [Mnn+1 (GlyGly-H)2n ](2+) charged clusters are formed from aqueous solutions of MnCl2 and GlyGly by electrospray ionization. The most intense ion produced was the singly charged [M2 (GlyGly-H)3 ](+) cluster. Singly charged clusters show extensive fragmentations of small neutral molecules such as water and carbon dioxide as well as dissociation pathways related to the loss of NH2 CHCO and GlyGly. For the doubly charged clusters, however, loss of GlyGly is observed as the main dissociation pathway. Structure elucidation of [Mn3 (GlyGly-H)4 ](2+) clusters has also been done by IRMPD spectroscopy as well as DFT calculations. It is shown that the lowest energy structure of the [Mn3 (GlyGly-H)4 ](2+) cluster is deprotonated at all carboxylic acid groups and metal ions are coordinated with carbonyl oxygen atoms, and that all amine nitrogen atoms are hydrogen bonded to the amide hydrogen. A comparison of the calculated high-spin (sextet) and low-spin (quartet) state structures of [Mn3 (GlyGly-H)4 ](2+) is provided. IRMPD spectroscopic results are in agreement with the lowest energy high-spin structure computed. Also, the gas-phase reactivity of these complexes towards neutral CO and water was investigated. The parent complexes did not add any water or CO, presumably due to saturation at the metal cation. However, once some of the ligand was removed via CO2 laser IRMPD, water was seen to add to the complex. These results are consistent with high-spin Mn(2+) complexes.

Estimating the DNA strand breakage using a fuzzy inference system and agarose gel electrophoresis, a case study with toothed carp Aphanius sophiae exposed to cypermethrin.

The DNA breakage has been widely used in ecotoxicological studies to investigate effects of pesticides in fishes. The present study used a fuzzy inference system to quantify the breakage of DNA double strand in Aphanius sophiae exposed to the cypermethrin. The specimens were adapted to different temperatures and salinity for 14 days and then exposed to cypermethrin. DNA of each specimens were extracted, electrophoresed and photographed. A fuzzy system with three input variables and 27 rules were defined. The pixel value curve of DNA on each gel lane was obtained using ImageJ. The DNA breakage was quantified using the pixel value curve and fuzzy system. The defuzzified values were analyzed using a three-way analysis of variance. Cypermethrin had significant effects on DNA breakage. Fuzzy inference systems can be used as a tool to quantify the breakage of double strand DNA. DNA double strand of the gill of A. sophiae is sensitive enough to be used to detect cypermethrin in surface waters in concentrations much lower than those reported in previous studies.

Self-Assembled Multimetallic/Peptide Complexes: Structures and Unimolecular Reactions of [Mn (GlyGly-H)2n-1 ](+) and Mn+1 (GlyGly-H2n ](2+) Clusters in the Gas Phase.

The unimolecular chemistry and structures of self-assembled complexes containing multiple alkaline-earth-metal dications and deprotonated GlyGly ligands are investigated. Singly and doubly charged ions [Mn (GlyGly-H)n-1 ](+) (n=2-4), [Mn+1 (GlyGly-H)2n ](2+) (n=2,4,6), and [M(GlyGly-H)GlyGly](+) were observed. The losses of 132 Da (GlyGly) and 57 Da (determined to be aminoketene) were the major dissociation pathways for singly charged ions. Doubly charged Mg(2+) clusters mainly lost GlyGly, whereas those containing Ca(2+) or Sr(2+) also underwent charge separation. Except for charge separation, no loss of metal cations was observed. Infrared multiple photon dissociation spectra were the most consistent with the computed IR spectra for the lowest energy structures, in which deprotonation occurs at the carboxyl acid groups and all amide and carboxylate oxygen atoms are complexed to the metal cations. The N-H stretch band, observed at 3350 cm(-1) , is indicative of hydrogen bonding between the amine nitrogen atoms and the amide hydrogen atom. This study represents the first into large self-assembled multimetallic complexes bound by peptide ligands.

Embedding piezoresistive pressure sensors to obtain online pressure profiles inside fiber composite laminates.

The production of large and complex parts using fiber composite materials is costly due to the frequent formation of voids, porosity and waste products. By embedding different types of sensors and monitoring the process in real time, the amount of wastage can be significantly reduced. This work focuses on developing a knowledge-based method to improve and ensure complete impregnation of the fibers before initiation of the resin cure. Piezoresistive and capacitive pressure sensors were embedded in fiber composite laminates to measure the real-time the pressure values inside the laminate. A change of pressure indicates resin infusion. The sensors were placed in the laminate and the resin was infused by vacuum. The embedded piezoresistive pressure sensors were able to track the vacuum pressure in the fiber composite laminate setup, as well as the arrival of the resin at the sensor. The pressure increase due to closing the resin inlet was also measured. In contrast, the capacitive type of sensor was found to be inappropriate for measuring these quantities. The following study demonstrates real-time monitoring of pressure changes inside the fiber composite laminate, which validate the use of Darcy's law in porous media to control the resin flow during infusion.

An L-Arginine supplement improves broiler hypertensive response and gut function in broiler chickens reared at high altitude.

An experiment was carried out to examine the effects of supplemental dietary arginine (ARG) on growth, hypertensive response, and gut function in broilers reared at high altitude (2,100 m). A total of 120 day-old male broilers (Cobb 500) were divided equally into two treatment groups. Treatments included a control basal diet composed of corn and soybean meal and an experimental diet to which an L-ARG supplement was added at 10 g/kg. The trial lasted for 42 days. There were no treatment differences with regard to feed intake, body weight gain, or feed conversion ratio. However ARG supplementation did increase the plasma concentration of nitric oxide, a potent vasodilator (P<0.05), and attenuated indices of pulmonary hypertension as reflected by reductions in the hematocrit and the right to total ventricular weight ratio (P<0.05). Significantly enhanced intestinal mucosal development was observed in broilers receiving ARG supplement when compared with controls (P<0.05), suggesting that ARG supplementation increased the absorptive surface area of the jejunum and ileum. In conclusion, broiler diets supplemented with ARG beneficially improved pulmonary hemodynamics and appeared to enhance gut function.

Comparison of the binding behavior of FCCP with HSA and HTF as determined by spectroscopic and molecular modeling techniques.

The interaction of carbonylcyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) with human serum albumin (HSA) and human transferrin (HTF) was investigated using multiple spectroscopy, molecular modeling, zeta-potential and conductometry measurements of aqueous solutions at pH 7.4. The fluorescence, UV/vis and polarization fluorescence spectroscopy data disclosed that the drug-protein complex formation occurred through a remarkable static quenching. Based on the fluorescence quenching, two sets of binding sites with distinct affinities for FCCP existed in the two proteins. Steady-state and polarization fluorescence analysis showed that there were more affinities between FCCP and HSA than HTF. Far UV-CD and synchronous fluorescence studies indicated that FCCP induced more structural changes on HSA. The resonance light scattering (RLS) and zeta-potential measurements suggested that HTF had a greater resistance to drug aggregation, whereas conductometry measurements expressed the presence of free ions improving the resistance of HSA to aggregation. Thermodynamic measurements implied that a combination of electrostatic and hydrophobic forces was involved in the interaction between FCCP with both proteins. The phase diagram plots indicated that the presence of second binding site on HSA and HTF was due to the existence of intermediate structures. Site marker competitive experiments demonstrated that FCCP had two distinct binding sites in HSA which were located in sub-domains IIA and IIIA and one binding site in the C-lobe of HTF as confirmed by molecular modeling. The obtained results suggested that both proteins could act as drug carriers, but that the HSA potentially had a higher capacity for delivering FCCP to cancerous tissues.

Stem cell-based therapy for systemic lupus erythematous.

Systemic lupus erythematosus (SLE), an autoimmune disease, is among the most prevalent rheumatic autoimmune disorders. It affects autologous connective tissues caused by the breakdown of self-tolerance mechanisms. During the last two decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including parkinson's disease, alzheimer, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabete, heart disease, bone disease, renal disease, respiratory diseases, and hematological abnormalities such as anemia. This is due to the unique properties of stem cells that divide and differentiate to the specialized cells in the damaged tissues. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders. In the present manuscript, efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cell (MSC), and hematopoietic stem cells (HSC) in animal models or human patients of SLE, has been reviewed. Taken together, MSC and HSC therapies improved the disease activity, and severity in kidney, lung, liver, and bone (improvement in the clinical manifestation). In addition, a change in the immunological parameters occurred (improvement in immunological parameters). The level of autoantibodies, including antinuclear antibody (ANA), and anti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) reduced. A conversion of Th1/Th2 ratio (in favor of Th2), and Th17/Treg (in favor of Treg) was also detected. In spite of many advantages of MSC and HSC transplantations, including efficacy, safety, and increased survival rate of SLE patients, some complications, including recurrence of the disease, occurrence of infections, and secondary autoimmune diseases (SAD) were observed after transplantation that should be addressed in the next studies.

The Efficacy of Different Antibiotic Compounds in Regenerative Treatment of Immature Necrotic Teeth.

Objectives: Endodontic treatment of immature teeth poses a significant challenge, especially in achieving a proper seal using traditional obturation methods. Revascularization presents itself as an alternative approach to this problem, and the application of triple antibiotic paste (TAP) has been suggested as a means to achieve disinfection during the procedure. This study aims to compare the antibacterial properties of three different antibiotic combinations to assess their effectiveness on root canal disinfection. Materials and Methods: Eighty samples were employed to assess the impact of three antibiotic combinations on Enterococcus faecalis, Escherichia coli, Streptococcus mutans, and a combination thereof. The antibiotics included metronidazole, ciprofloxacin, and cefaclor (CCM), the commonly used TAP, and a double antibiotic paste (DAP) composed of metronidazole and ciprofloxacin. Dentin shavings collected using Gates-Glidden drills were placed in microtubes containing a 2ml standard bacterial suspension. Microtube contents were diluted and cultured on BHI agar plates, with colony counts calculated based on dentine shavings' weight in CFU/mg. Kruskal-Wallis and Dunn's post-hoc tests were used for statistical analysis and P<0.05 was considered significant. Results: A significant difference in mean CFU was observed among all bacterial groups (P<0.05). Dunn's post-hoc analysis showed a significant difference only between the control group (methylcellulose) and the other antibiotic groups. There was no significant difference between the other antibiotic groups in two-by-two comparisons. Conclusion: There was no significant difference in the antimicrobial properties of DAP, TAP and CCM. Therefore, DAP and CCM may be used during regenerative treatment.

The wound healing effect of polycaprolactone-chitosan scaffold coated with a gel containing Zataria multiflora Boiss. volatile oil nanoemulsions.

AIMS: Thymus plant is a very useful herbal medicine with various properties such as anti-inflammatory and antibacterial. Therefore, the properties of this plant have made this drug a suitable candidate for wound healing. In this study, hydroxypropyl methylcellulose (HPMC) gel containing Zataria multiflora volatile oil nanoemulsion (neZM) along with polycaprolactone/chitosan (PCL-CS) nanofibrous scaffold was used, and the effect of three experimental groups on the wound healing process was evaluated. The first group, HPMC gel containing neZM, the second group, PCL-CS nanofibers, and the third group, HPMC gel containing neZM and bandaged with PCL-CS nanofibers (PCL-CS/neZM). Wounds bandaged with common sterile gas were considered as control. METHODS: The nanoemulsion was synthesized by a spontaneous method and loaded into a hydroxypropyl methylcellulose (HPMC) gel. The DLS test investigated the size of these nanoemulsions. A PCL-CS nanofibrous scaffold was also synthesized by electrospinning method then SEM and contact angle tests investigated morphology and hydrophilicity/hydrophobicity of its surface. The animal study was performed on full-thickness skin wounds in rats, and the process of tissue regeneration in the experimental and control groups was evaluated by H&E and Masson's trichrome staining. RESULTS: The results showed that the nanoemulsion has a size of 225±9 nm and has an acceptable dispersion. The PCL-CS nanofibers synthesized by the electrospinning method also show non-beaded smooth fibers and due to the presence of chitosan with hydrophilic properties, have higher surface hydrophobicity than PCL fibers. The wound healing results show that the PCL-CS/neZM group significantly reduced the wound size compared to the other groups on the 7th, 14th, and 21st days. The histological results also show that the PCL-CS/neZM group could significantly reduce the parameters of edema, inflammation, and vascularity and increase the parameters of fibrosis, re-epithelialization, and collagen deposition compared to other groups on day 21. CONCLUSION: The results of this study show that the PCL-CS/neZM treatment can effectively improve wound healing.

Human-derived Tumor-On-Chip model to study the heterogeneity of breast cancer tissue.

One of the leading causes that complicate the treatment of some malignancies, including breast cancer, is tumor heterogeneity. In addition to inter-heterogeneity and intra-heterogeneity of tumors that reflect the differences between cancer cell characteristics, heterogeneity in the tumor microenvironment plays a critical role in tumor progression and could be considered an overlooked and a proper target for the effective selection of therapeutic approaches. Due to the difficulty of completely capturing tumor heterogeneity in conventional detection methods, Tumor-on-Chip (TOC) devices with culturing patient-derived spheroids could be an appropriate alternative. In this research, human-derived spheroids from breast cancer individuals were cultured for 6 days in microfluidic devices. To compare TOC data with conventional detection methods, immunohistochemistry (IHC) and ITRAQ data were employed, and various protein expressions were validated using the transcriptomic databases. The behavior of the spheroids in the collagen matrix and the cell viability were monitored over 6 days of culture. IHC and immunocytochemistry (ICC) results revealed that inter and intra-heterogeneity of tumor spheroids are associated with HER2/ER expression. HER2 expression levels revealed a more important biomarker associated with invasion in the 3D culturing of spheroids. The expression levels of CD163 (as a marker for Ma2 macrophages) and CD44 (a marker for cancer stem cells (CSCs)) were also evaluated. Interestingly, the levels of M2a macrophages and CSCs were higher in triple-negative specimens and samples that showed higher migration and invasion. Cell density and extracellular matrix (ECM) stiffness were also important factors affecting the migration and invasion of the spheroids through the matrix. Among these, rigid ECM revealed a more crucial role than cell density. To sum up, these research findings demonstrated that human-derived spheroids from breast cancer specimens in microfluidic devices provide a dynamic condition for predicting tumor heterogeneity in patients, which can help move the field forward for better and more accurate therapeutic strategies.

Use of Albumin for Drug Delivery as a Diagnostic and Therapeutic Tool.

Drug delivery is an important topic that has attracted the attention of researchers in recent years. Albumin nanoparticles play a significant role in drug delivery as a carrier due to their unique characteristics. Albumin is non-toxic, biocompatible, and biodegradable. Its structure is such that it can interact with different drugs, which makes the treatment of the disease faster and also reduces the side effects of the drug. Albumin nanoparticles can be used in the diagnosis and treatment of many diseases, including cancer, diabetes, Alzheimer's, etc. These nanoparticles can connect to some compounds, such as metal nanoparticles, antibodies, folate, etc. and create a powerful nanostructure for drug delivery. In this paper, we aim to investigate albumin nanoparticles in carrier format for drug delivery application. In the beginning, different types of albumin and their preparation methods were discussed, and then albumin nanoparticles were discussed in detail in diagnosing and treating various diseases.

Stem cell-based therapy for systemic sclerosis.

Autoimmune diseases, including SSc, are prevalent, affecting autologous connective tissues and caused by the breakdown of self-tolerance mechanisms of the immune system. During the last 2 decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including Parkinson's disease, Alzheimer's disease, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabetes, heart disease, bone disease, renal disease, respiratory disease and haematological abnormalities such as anaemia. This is due to the unique properties of stem cells that both divide and differentiate to the specialized cells in the damaged tissue. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as SSc. In the present review, the efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cells and hematopoietic stem cells, will be reviewed. Moreover, other related issues, including safety, changes in immunological parameters, suitable choice of stem cell origin, conditioning regimen and complications of stem cell treatment will be discussed.