Layered dermal reconstitution through epigallocatechin 3-gallate loaded chitosan nanoparticle within enzymatically crosslinked polyvinyl alcohol/collagen fibrous mat.

Biocompatible electrospun fiber comprising bioactive substrates has potential to implant into the wound site as a reliable therapeutic approach in tissue regeneration. Here, electrospun polyvinyl alcohol conjugated tyramine (PVA-Tyr) and collagen (Col) fibrous mat containing chitosan nanoparticle loaded with epigallocatechin 3-gallate (NCs-EGCG) developed and the composite was applied to evaluate in vivo wound healing ability of fabricated wound patch. The synthesized PVA-Tyr and Col were electrospun and crosslinked through peroxidase reaction in presence of vaporized H2O2 as an electron donor which covalently proceeded conjugation of phenolic groups and could develop hybrid fibrous mat in stable structure and uniform shapes. The EGCG as anti-oxidative/inflammatory substrate was encapsulated efficiently in NCs and released in a sustained manner. The hybrid fibers seeded with adipose-derived stem cells presented appropriate biocompatibility from biophysical and biochemical viewpoints and in following wound healing ability in a full-thickness excisional animal model. Fourier transform infrared spectroscopy (FTIR) confirmed all typical absorption characteristics of PVA-Tyr and Col as well as NCs and EGCG. The results showed the perfect hydrophilic/hydrophobic ratio and good mechanical and structural characteristics including shape uniformity and porosity. Interestingly, cellular attachment and proliferation on the PVA-Tyr/Col fibers containing NCs-EGCG were higher than control samples. The histological analysis of hybrid fibrous patch could be suggested the applicability of this structure as suitable skin substitutes to repair injured skin.

Identification and detection of pathogenic bacteria from patients with hospital-acquired pneumonia in southwestern Iran; evaluation of biofilm production and molecular typing of bacterial isolates.

BACKGROUND: Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection in intensive care units (ICUs). The present study aims to determine the prevalence of pathogenic bacteria, their biofilm formation, and molecular typing from patients with HAP in southwestern Iran. METHODS: Fifty-eight patients with HAP participated in this cross-sectional study. Sputum and endotracheal aspirate were collected from each patient for isolation and detection of bacteria. Biofilm formation was evaluated using Congo red agar or Microtiter plate assay. The antimicrobial susceptibility patterns of the isolates were investigated. The multiplex polymerase chain reaction (M-PCR) technique was used to determine the Staphylococcal Cassette Chromosome mec (SCCmec) types of methicillin-resistant Staphylococcus aureus (MRSA) strains. All S. aureus isolates were typed using the agr typing method. A repetitive element sequence-based PCR (rep-PCR) typing method was used for typing of Gram-negative bacteria. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software version 15 and the chi-square test. RESULTS: Bacteria were isolated in 52 (89.7%) of patients. Acinetobacter baumannii (A. baumannii) was the most prevalent organism (37%), followed by S. aureus, Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli). Using the PCR method, 56 bacteria were detected. A. baumannii was the most prevalent (35.7%) organism. A. baumannii and P. aeruginosa were biofilm-producing. All Gram-negative isolates were colistin-sensitive, and most of the A. baumannii isolates were multidrug-resistant (MDR). MRSA was identified in 12 (80%) S. aureus isolates, and 91.6% of MRSA were SCCmec type III. The agr type III was the most predominant. The rep-PCR analysis showed seven different patterns in 20 A. baumannii, six patterns in 13 P. aeruginosa, and four patterns in 6 E. coli. CONCLUSION: A. baumannii was more prevalent than S. aureus in ventilator-associated pneumonia (VAP), while S. aureus is a major pathogen in non-ventilator hospital-acquired pneumonia (NV-HAP), possibly due to the tendency of the former to aquatic environments. Based on the rep-PCR typing method, it was concluded that bacteria were transmitted from patients or healthcare workers among different wards. Colistin can be used as a treatment in Gram-negative MDR isolates.

Patients with Covid 19 have significantly reduced CH50 activity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a new virus that emerged in China and immediately spread around the world. Evidence has been documented that the immune system is impressively involved in the pathogenesis of this disease, especially in causing inflammation. One of the important components of the immune system is the complement system whose increased activity has been shown in inflammatory diseases and consequently damage caused by the activity of its components. In the present study, serum levels of C3 and C4 factors as well as the activity level of complement system in the classical pathway were measured by CH50 test in patients with SARS-CoV-2. Participants in the study consisted of 53 hospitalized patients whose real-time PCR test was positive for SARS-CoV-2. The mean age of these patients was 42.06 ± 18.7 years, including 40% women and 60% men. The most common symptoms in these patients were cough (70%), fever (59%), dyspnea (53%) and chills (53%), respectively. Analysis of biochemical and hematological test results revealed that 26 (49%) patients had lymphopenia, 34 (64%) patients were positive for C-reactive protein (CRP) and 26 (49%) patients had ESR and LDH levels significantly higher than normal. In addition, 27 patients (51%) had vitamin D deficiency. The mean CH50 activity level in COVID-19 patients was significantly reduced compared to healthy individuals (84.9 versus 169.9 U/ml, p = < 0.0001). Comparison of the mean CH50 activity levels between different subgroups of patients indicated that COVID-19 patients with decreased peripheral blood lymphocyte count and positive CRP had a significant increase in activity compared to the other groups (p = 0.0002). The serum levels of C3 and C4 factors had no significant change between patients and healthy individuals. Conclusion: The activity level of complement system in the classical pathway decreases in COVID-19 patients compared to healthy individuals, due to increased activity of complement system factors in these patients.

Silencing of IL-6 and STAT3 by siRNA loaded hyaluronate-N,N,N-trimethyl chitosan nanoparticles potently reduces cancer cell progression.

The immunosuppressive nature of the tumor microenvironment is a critical problem that should be considered before the design of immunotherapies. Interleukin (IL)-6 and its related downstream molecules such as signal transducer and activator of transcription (STAT)3 play an important role in the cancer progression, which can be considered as potential therapeutic targets. In the present study, we generated the active-targeted hyaluronate (HA) recoated N, N, N-trimethyl chitosan (TMC) nanoparticles (NPs) to deliver IL-6- and STAT3-specific small interfering RNAs (siRNAs) to the CD44-expressing cancer cells. We utilized the interaction between HA and CD44 to increase the specificity and efficacy of cellular uptake in NPs. The results showed that the synthesized NPs had efficient physicochemical characteristics, high transfection efficiency, low toxicity, and controlled siRNA release. siRNA-loaded NPs significantly inhibited the IL-6/STAT3 expression, which was associated with blockade of proliferation, colony formation, migration, and angiogenesis in cancer cells. These findings imply the potential of HA-TMC NPs as potent vectors in gene therapy and their application for the silencing of IL-6 and STAT3, as a novel anti-cancer combination therapeutic strategy, for the first time.

Blockage of immune checkpoint molecules increases T-cell priming potential of dendritic cell vaccine.

Dendritic cell (DC) -based cancer immunotherapy is one of the most important anti-cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well-known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD-L1) on DCs, which interacts with PD-1 on T cells, leads to inhibition of anti-tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down-regulation of PD-L1 in DCs in association with silencing of PD-1 on T cells may lead to the enhancement of T-cell priming by DCs to have efficient anti-tumor T-cell responses. In this study, we silenced the expression of PD-L1 in DCs and programmed cell death protein 1 (PD-1) in T cells by small interfering RNA (siRNA) -loaded chitosan-dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T-cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD-L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD-L1-negative DCs to PD-1-silenced T cells led to induction of potent T-cell responses. Our findings imply that PD-L1-silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD-1-siRNA loaded NPs, however; further in vivo investigation is required in animal models.

Epstein-Barr virus hepatitis can cause transient hepatopulmonary syndrome.

INTRODUCTION: Hepatopulmonary syndrome is commonly seen in the patients with chronic liver disease. Acute liver diseases are rarely associated with HPS. We have reported here a case of Transient HPS caused by Epstein-Barr virus hepatitis. CASE REPORT: The patient was a 31 years old man that came to hospital due to RUQ pain and yellowish skin. In examination the patient was tachypnic and O2 saturation was 71% with prominent JVP. ver enzyme and bilirubin were high. All viral hepatitis was negative except anti viral capsid antigen-antibody of EBV. In Blood gas PaO2 was 54 mmHg, O2 saturation 73% and alveolar-arterial gradient was 18 mmHg. Stress Echocardiography with saline injection reported pulmonary arterial pressure 32 cmHg with delayed opacification of left atrium. CONCLUSION: transient HPS can be manifestation in the acute hepatitis caused by EBV infection.

Case Report: Pulmonary and Liver Sarcoidosis Suspected of Metastasis.

Introduction: Sarcoidosis is a granulomatous disease with unknown cause that can vary from an asymptomatic condition. Almost half of the patients with sarcoidosis have no symptoms. In this article, we describe a sarcoidosis patient with lung and liver engagement; it may be confused with metastasis. Case report: A 39-year-old man, known as hypothyroidism who had come to the emergency ward with dyspnea and coughing after exposure to detergents in a closed environment A 39-year-old man, known as hypothyroidism who had come to the emergency ward with dyspnea and coughing after exposure to detergents in a closed environment. The patient smoked for 10 years (3 pack/year). No other findings were found in clinical examinations except for wheezing in the right lung. The patient's chest radiography was shown a mass. For further investigation, spiral CT scan was performed. Large lymph nodes on the right side of the trachea, measuring about 23 mm and a mass of 70 × 77 mm in the vicinity of the right lung hilum and a hypodense nodule in the posterior part of the liver with malignancy suspicious were reported. After several biopsy results was shown chronic granulomatous inflammation, the most important differential diagnosis is tuberculosis (TB) and sarcoidosis. Sputum smear, culture, and PCR were performed for tuberculosis. Also, the level of angiotensin-converting enzyme (ACE) was measured for sarcoidosis. the results ruled out TB and shown a higher level of ACE (ACE = 88).After diagnosis treatment started with prednisolone. Now, the patient is in the follow- up. Conclusion: In hilar lymphadenopathy of lung sarcoidosis is the importance differential diagnosis that should be considered.

Case Report: Polyarteritis nodosa or complicated Henoch-Schonlein purpura (IgAV), a rare case.

Background: Polyarteritis nodosa (PAN) is a vasculitis that affects medium sized arteries. PAN is a rare disease and requires a high vilgilance for diagnosis. For instance, PAN and Henoch-Schonlein purpura (HSP) have narrowing differential diagnosis. Here, we report a case of PAN. Case presentation: Our patient was a 65 year old woman that came to hospital due to abdominal pain and skin lesion on the right upper and right lower extremities. All rheumatologic tests were negative. A biopsy of the skin lesion was reported as mild hyperkeratosis, slight spongiosis with intact basal layer. The dermis showed moderate to severe perivascular PMN infiltration with vessel wall degeneration and extravasation of RBCs. A colonoscopy reported diffuse mucosal erythema and erosions were seen in the rectum until 6cm of anal verge. An electromyogram test and nerve conduction velocity study of the upper extremities reported bilateral mild carpal tunnel syndrome, and in the right lower extremities mononeuritis multiplex could not be ruled out. Abdominopelvic CT scan reported diffuse wall thickening of terminal ileum associated with mesenteric fat and narrow enhancement of inferior Mesenteric artery with patchy filling defect. After evaluation, the patient received corticosteroid pulses plus cyclophosphamide. Conclusion: Diagnosis and treatment of PAN is important and PAN should be considered in a patient with skin lesions and neurological impairment.