Current knowledge on therapeutic, diagnostic, and prognostics applications of exosomes in multiple myeloma: Opportunities and challenges.

Interactions between the plasma cells and the BM microenvironment of Multiple myeloma (MM) take place through factors such as exosomes. Many studies have confirmed the role of exosomes in these interactions. By carrying proteins, cytokines, lipids, microRNAs, etc. as their cargo, exosomes can regulate the interactions between MM plasma cells and neighboring cells and participate in the signaling between cancer cells and the environment. It has been shown that MM-derived exosomes can induce angiogenesis, enhance osteoblast activity, confer drug resistance, and have immunosuppressive properties. Abnormal cargos in endosomes originating from MM patients, can be used as a cancer biomarker to detect or screen early prognosis in MM patients. The native nanostructure of exosomes, in addition to their biocompatibility, stability, and safety, make them excellent candidates for therapeutic, drug delivery, and immunomodulatory applications against MM. On the other hand, exosomes derived from dendritic cells (DC) may be used as vaccines against MM. Thanks to the development of new 'omics' approaches, we anticipate to hear more about exosomes in fight against MM. In the present review, we described the most current knowledge on the role of exosomes in MM pathogenesis and their potential role as novel biomarkers and therapeutic tools in MM.

Mining the soil myxobacteria and finding sources of anti-diabetic metabolites.

Secondary metabolites produced by myxobacterial genera are often characterized as diverse molecules with unique structural properties which drove us to search for myxobacterial source of anti-diabetic drug discovery. In the present study, from 80 soil samples, out of sixty-five observed isolates, 30 and 16 were purified as Myxococcus and non-Myxococcus, respectively. Isolated strains taxonomically belonged to the genera Myxococcus, Corallococcus and Cystobacter, Archangium, Nanocystis, and Sorangium, and some could not be attributed. Secondary metabolites of selected non-Myxococcus isolates extracted by the liquid-liquid method showed that the myxobacterium UTMC 4530 demonstrated the highest inhibition on the formation of carbonyl group and fructosamine, respectively. In addition, it showed 23% and 15.8% inhibitory activity on α-glucosides and α-amylase compared to acarbose (23%, 18%), respectively. The extract of strain UTMC 4530 showed 35% induction effect on glucose adsorption while showing no radical scavenging activity and no toxic effect on HRBC lysis and HepG2 in cytotoxicity assays. The strain UTMC 4530 (ON808962), with the multiple antidiabetic activity, showed 87.3% similarity to Corallococcus llansteffanensis which indicates its affiliation to a new genus. The results of this study revealed that secondary metabolites produced by strain UTMC 4530 can be considered a promising source to find new therapeutic and pharmaceutical applications perhaps a multi-mechanism anti-diabetic compound.

Biogenesis, inheritance, and 3D ultrastructure of the microsporidian mitosome.

During the reductive evolution of obligate intracellular parasites called microsporidia, a tiny remnant mitochondrion (mitosome) lost its typical cristae, organellar genome, and most canonical functions. Here, we combine electron tomography, stereology, immunofluorescence microscopy, and bioinformatics to characterise mechanisms of growth, division, and inheritance of this minimal mitochondrion in two microsporidia species (grown within a mammalian RK13 culture-cell host). Mitosomes of Encephalitozoon cuniculi (2-12/cell) and Trachipleistophora hominis (14-18/nucleus) displayed incremental/non-phasic growth and division and were closely associated with an organelle identified as equivalent to the fungal microtubule-organising centre (microsporidian spindle pole body; mSPB). The mitosome-mSPB association was resistant to treatment with microtubule-depolymerising drugs nocodazole and albendazole. Dynamin inhibitors (dynasore and Mdivi-1) arrested mitosome division but not growth, whereas bioinformatics revealed putative dynamins Drp-1 and Vps-1, of which, Vps-1 rescued mitochondrial constriction in dynamin-deficient yeast (Schizosaccharomyces pombe). Thus, microsporidian mitosomes undergo incremental growth and dynamin-mediated division and are maintained through ordered inheritance, likely mediated via binding to the microsporidian centrosome (mSPB).

Isolation and characterization of a bisphenol A-degrading strain, Pseudomonas aeruginosa DU2, from soil containing decaying plants.

Background and Objectives: Bisphenol A (BPA) is a toxic compound with broad applications in the plastics industry. BPA has harmful effects on various organisms and its efficient removal is necessary. The microbial degradation of BPA is a safe and economical approach. In this research, soil samples containing decaying plants were screened to isolate a BPA-degradable bacterial strain. Materials and Methods: Soil samples were collected from different locations in Damghan, Semnan province, Iran. To enrich BPA-degrading bacteria, the samples were cultured in a stepwise manner in a mineral medium containing increasing BPA concentrations (5 to 40 mg/L). The ability of isolated bacteria in degrading BPA was assayed by Folin-Ciocalteu and high-performance liquid chromatography methods. The biodegradation efficiency of the most efficient isolate was assayed under distinct conditions and it was identified through the sequencing of the 16S rRNA gene. Results: Among the isolated bacteria, Pseudomonas aeruginosa DU2 (GenBank accession number: OP919484) showed the most BPA biodegradation ability. The highest BPA degradation (52.98%) was observed in the mineral medium containing 5 mg/L BPA and the inoculum size of 6 × 107 CFU/mL at pH 9 and in the presence of 0.05% (w/v) NaCl during 10 days. Conclusion: These results offer soil containing decaying plants as a promising source for finding BPA-degrading bacteria. P. aeruginosa DU2 has basal BPA removal ability, which could be improved by optimization of medium components and growth conditions.

Effectiveness of Phosphate and Zinc Solubilizing Paenarthrobacter nitroguajacolicus P1 as Halotolerant Rhizobacterium with Growth-Promoting Activity on Pistacia vera L.

Plant growth-promoting rhizobacteria (PGPR) are beneficial microorganisms to develop microbial fertilizers. Biofertilizers can accelerate plant growth and enhance crop yields. The current research aimed to isolate and identify rhizobacterium with plant growth-promoting activity in the rhizospheric region of pistachio trees in arid and salty region of Iran. In the present study, 26 bacterial isolates were isolated from the rhizospheric region of the pistachio trees. Plant growth-promoting characteristics of isolated bacteria, including the ability to solubilize phosphate and zinc, produce hydrolyzing enzymes, and hydrogen cyanide (HCN), as well as synthesize indole-3-acetic acid (IAA) were evaluated through in vitro assays. Based on these activities, five multifunctional bacterial strains designated P1, P10, P11, P17, and P19 were then applied and their effect was studied on the growth and physiological properties of Pistacia vera L. seedlings by pot experiments under normal conditions. Finally, the most efficient strain has been identified by analysis of the 16S rRNA gene sequence. According to the results, all the isolated bacteria exhibited considerable plant growth-promoting properties. They could produce amylase (n = 26, 2 ± 0.00-13 ± 0.42 mm), lipase (n = 24, 2 ± 0.00-9 ± 0.23 mm), protease (n = 20, 1 ± 0.00-17 ± 0.0 mm), indole-3-acetic acid (n = 26, ranging from 5.05 ± 0.08 to 11.5 ± 0.11 µg/mL) and HCN (n = 24). Six isolates showed significant growth at 20% w/v NaCl. Inoculation of P1, P17, and P19 increased chlorophyll, carotenoid, and phenolic content in treated Pistacia vera L. seedlings. P1 and P11 inoculated plants showed an enhanced level of anthocyanin and proline. These most effective strains were catalase and Gram-positive bacterium and showed antibiotic sensitivity. They can consider as halotolerant PGPR, due to the growth in the presence of NaCl (20% w/v). Finally, P1 inoculated plants exhibited higher levels of sugar content. This strain showed the most similarity (99.92%-1322 bp) to Paenarthrobacter nitroguajacolicus based on 16S rRNA gene sequence. Based on the results, Paenarthrobacter nitroguajacolicus P1 with multiple PGPR can be applied as a promising candidate in the soil-Pistacia vera L. system to improve their productivity and health by increasing available nutrient content, improving photosynthetic parameters, and producing phytohormones and HCN.

CoFe2O4@SiO2-NH2@MOF-5 magnetic nanocatalyst for the synthesis of biologically active quinazoline derivatives.

Metal-organic frameworks (MOFs) offered excellent catalytic activity due to their superior porosity, and high densities of catalytic sites in remarkable specific surfaces. In this research, we prepared a magnetic nanocomposite based on MOF-5 which is one of the prominent and practical structures that have been reported in many applications, and investigated the advantages of it as a catalyst. The multi-functional catalyst was prepared in five steps including (1) preparation of cobalt ferrite nanoparticles (CoFe2O4), (2) surface modification of cobalt ferrite using tetraethyl orthosilicate, (3) surface functionalization using 3-aminopropyl triethoxysilane, (4) preparation of MOF-5, (5) preparation of CoFe2O4@SiO2-NH2@MOF-5 nanocomposite. The resulting catalyst was evaluated by FTIR, FESEM, EDX, XRD, and VSM analyses. The CoFe2O4@SiO2-NH2@MOF-5 nanocomposite was applied as a catalyst for the quinazoline derivatives' synthesis. Various products were prepared with significant yields (90-98%) in short reaction times (20-60 min) without difficult work-up. In addition, the magnetic behavior of the catalyst allows it to be collected and recycled by a magnet and applied for six consecutive cycles without significantly reducing its efficiency. Quinazoline derivatives showed significant biological activities so their antioxidant activity was between 23.7% and 88.9% and their antimicrobial activity was in contradiction of E. coli, S. enterica, L. monocytogenes, S. aureus, and E. faecalis.

Recent advances in the biological activities of microbial exopolysaccharides.

Microbial exopolysaccharides (EPSs) are valuable extracellular macromolecules secreted as capsules or slime layers. Various microorganisms, including bacteria, yeasts, fungi, and algae have been studied for their ability to produce EPSs. Microbial EPSs exist as homopolysaccharides or heteropolysaccharides with various properties such as different monosaccharide compositions, structural conformation, molecular weight, and functional groups. They are cost-effective alternatives to plant and animal-derived polysaccharides because the microbial cells produced them in large quantities by biotechnological processes using low-cost substrates such as industrial wastes in a short time. Microbial EPSs are safe, biodegradable, and compatible polymers. They have extensive bioactivities, including antibacterial, antifungal, antiviral, antioxidant, antitumor, antidiabetic, antiulcer, anticoagulant, antiaging, immunomodulatory, wound healing, and cholesterol-lowering activities. Microbial EPSs owing to biological activities, special biochemical structures, and attractive physicochemical properties find plenty of potential applications in various industries. The enhancement of the production of EPSs and improving their properties can be provided by genetic engineering methods. The current review aims to provide a comprehensive examination of the therapeutic activities of microbial EPSs in infectious diseases and metabolic disorders, with a focus on the mechanisms involved. Also, the effect of the physicochemical characteristics of EPSs on these bioactivities was discussed to reveal the structure-activity relationship.

A 4 mm vesicoureteric junction stone causing rupture of pelvicoureteric junction - case report.

We discuss the case of a 67-year-old man who presented with a right-sided abdominal pain and on subsequent radiological imaging(s) in the form of an enhanced computed tomography scan of the abdomen and pelvis followed by a delayed excretory phase (computed tomography urogram), found to have a distal 4 mm vesicoureteric junction stone which had caused a pelvicoureteric junction rupture which was evident on extravasation of contrast. This warranted an urgent surgical intervention in the form of ureteric stent insertion. This case clearly depicts that with even a small stone associated with severe flank pain, rupture or pelvicoureteric junction/calyces should be suspected and we should never overlook symptoms and push for medical expulsive therapy in patients who do not appear to be septic or obstructed. This work has been reported in line with the Surgical CAse REport (SCARE) criteria.

Early sigmoid perforation involving left inguinal hernia mesh repair: a case report.

Injury to the underlying bowel is a serious potential complication following inguinal hernia mesh repair. Here the authors describe a rare case of a 69-year-old gentleman who initially presented with a deep collection in the retroperitoneum, which extended into the extraperitoneal space on the anterior abdominal wall 3 weeks following left inguinal hernioplasty. Early sigmoid perforation involving the inguinal hernia mesh repair was diagnosed, and he underwent a successful Hartmann's procedure with mesh removal.

Characterization of Probiotic Pichia sp. DU2-Derived Exopolysaccharide with Oil-in-Water Emulsifying and Anti-biofilm Activities.

Probiotic-derived exopolysaccharides are considered as promising sources of carbohydrate with extensive applications in many industries. In the current study, yeast strains were isolated from chicken ingluvies and gizzard samples. According to molecular identification, EPS-producing yeast (Pichia sp. DU2) showed the most similarity to Pichia cactophila (99.67%). Pichia sp. DU2 showed probiotic properties. EPS of Pichia sp. DU2 showed emulsifying activity. The formed emulsions showed 53% (colza oil) and 100% (p-xylene) stability after 24 h. These emulsions were oil-in-water and have stability in the presence of NaCl, KCl, and also acidic and basic conditions. Also, the EPS showed anti-biofilm (29.7-47.6% and 19.06-55.26% against B. cereus and Y. enterocolitica, respectively) and flocculating activities (31.4%). FT-IR showed the presence of various functional groups in EPS structure. Also, its heteropolysaccharide nature was revealed in 1H-NMR and HPLC analysis. This emulsifying EPS showed significant thermal stability and negative zeta potential, which make it a promising carbohydrate for various industries. Finally, according to the predicted model, the maximal EPS production was achieved at reaction time 36 h, pH 6, yeast extract concentration 1.0%, and sucrose concentration 5%. Pichia sp. DU2 with probiotic properties and producing EPS with emulsifying, anti-biofilm, and flocculating activities can be considered as promising yeast strain in various industries like food and pharmaceutical industries.

Therapeutic potential of phospho-thiadiazole derivatives as anti-glioblastoma agents: synthesis, biological assessment and computational study.

In this study, three new phospho thiadiazole compounds (A, F and W) were investigated as possible cytotoxic agents. The compounds were synthesised and characterised by using spectroscopy methods. The crystal structure of compound A was investigated using X-ray crystallography, since the title compounds can exist as different tautomeric forms, their conformational and geometrical aspects were investigated computationally by the DFT method. NBO analysis suggested that these compounds can function as appropriate ligands for the reaction with the nitrogen bases of DNA. All the synthesised compounds were evaluated in vitro for their cytotoxic activities against cancer in the human glioblastoma cell lines (U-251) using the MTT assay. According to the annexin V-FITC/PI results, a combination of synthesised compounds with ReoT3D showed a synergistic effect to increase the percentage of apoptotic cells. Molecular docking study for A (the most toxic compound) showed how it interacts with DNA. Both in vitro and in silico results showed that A has promising inhibitory potential (IC50: 48.1 ± 0.3 µM) and binding energy (-6.67 kcal/mol).

Deep learning framework for prediction of infection severity of COVID-19.

With the onset of the COVID-19 pandemic, quantifying the condition of positively diagnosed patients is of paramount importance. Chest CT scans can be used to measure the severity of a lung infection and the isolate involvement sites in order to increase awareness of a patient's disease progression. In this work, we developed a deep learning framework for lung infection severity prediction. To this end, we collected a dataset of 232 chest CT scans and involved two public datasets with an additional 59 scans for our model's training and used two external test sets with 21 scans for evaluation. On an input chest Computer Tomography (CT) scan, our framework, in parallel, performs a lung lobe segmentation utilizing a pre-trained model and infection segmentation using three distinct trained SE-ResNet18 based U-Net models, one for each of the axial, coronal, and sagittal views. By having the lobe and infection segmentation masks, we calculate the infection severity percentage in each lobe and classify that percentage into 6 categories of infection severity score using a k-nearest neighbors (k-NN) model. The lobe segmentation model achieved a Dice Similarity Score (DSC) in the range of [0.918, 0.981] for different lung lobes and our infection segmentation models gained DSC scores of 0.7254 and 0.7105 on our two test sets, respectfully. Similarly, two resident radiologists were assigned the same infection segmentation tasks, for which they obtained a DSC score of 0.7281 and 0.6693 on the two test sets. At last, performance on infection severity score over the entire test datasets was calculated, for which the framework's resulted in a Mean Absolute Error (MAE) of 0.505 ± 0.029, while the resident radiologists' was 0.571 ± 0.039.

The impact of mental workload, work-related and socio-demographic factors on job burnout among emergency medical staff.

BACKGROUND: Job burnout syndrome is caused by prolonged exposure to difficult working conditions. Emergency medical services (EMS) staff are exposed to varying levels of mental workload (MWL) depending on the operation, so it is more likely that they experience burnout syndrome. OBJECTIVE: The main aim of the current research was to investigate the effect of MWL, work-related and socio-demographic factors on job burnout among Iranian EMS staff. METHODS: The current cross-sectional and descriptive-analytical research was carried out among 198 EMS. In doing so, the Maslach Burnout Inventory (MBI), The NASA task load index (NASA TLX), and an author-developed work-related and socio-demographic factors were distributed among participants to collect data. The data were analyzed using descriptive and inferential statistics (t-test, ANOVA test, multiple linear regression, and Pearson correlation coefficient). RESULTS: The results showed a significant statistical relationship between burnout and MWL. A significant statistical relationship between overall workload and two dimensions of MBI, namely, emotional exhaustion and depersonalization were observed (P < 0.05). Moreover, a significant statistical difference regarding the mean of burnout in the different groups of educational levels and occupational categories were observed. CONCLUSIONS: The EMS staff generally reported moderate levels of MWL and burnout. Findings showed that socio-demographic and occupational factors had little effect on burnout. MWL, education levels, and occupational categories are the main predictors of job burnout.

Characterization of exopolysaccharide produced by probiotic Enterococcus durans DU1 and evaluation of its anti-biofilm activity.

Exopolysaccharides (EPS) produced by lactic acid bacteria are complicated polymers with industrial applications. LAB were isolated, screened for EPS production, and their probiotic properties determined. The anti-biofilm activity of EPS was investigated. Safety of EPS-producing isolate was investigated and it was molecularly identified through 16S rRNA sequencing. Finally, anti-biofilm and emulsification activity of EPS was studied and it was characterized using FT-IR, TGA, 1H-NMR, DLS and HPLC. Thirteen LAB were isolated from dairy products. They showed probiotic characteristics like acid resistance (0-6.51 CFU ml-1) hydrophobicity (8-54.04%), autoaggregation (0% [t = 2 h]-99.8% [t = 24 h]) and coaggregation with food borne pathogens. Among them, Enterococcus durans DU1 had ability to produce EPS. EPS of Enterococcus durans DU1 showed antibiofilm activity against Y. enterocolitica (24.06-51.36%), S. aureus (12.33-49.6%), and B. cereus (11.66-27.16%). FT-IR showed this EPS had characteristic absorption peaks due to the presence of the pyran ring of sugars. 1H NMR showed that EPS has N-acetyl, methyl, and alkyl groups in its structure. The HPLC analysis showed that EPS is a heteropolysaccharide and consists of sucrose, glucose, and fructose. EPS showed significant thermal stability (20% weight loss) under 300 °C and zeta potential of - 18.1 mV. This EPS can be used in the food industry with no adverse effect on consumers.

Statistical analysis of COVID-19 infection severity in lung lobes from chest CT.

Detection of the COVID 19 virus is possible through the reverse transcription-polymerase chain reaction (RT-PCR) kits and computed tomography (CT) images of the lungs. Diagnosis via CT images provides a faster diagnosis than the RT-PCR method does. In addition to low false-negative rate, CT is also used for prognosis in determining the severity of the disease and the proposed treatment method. In this study, we estimated a probability density function (PDF) to examine the infections caused by the virus. We collected 232 chest CT of suspected patients and had them labeled by two radiologists in 6 classes, including a healthy class and 5 classes of different infection severity. To segment the lung lobes, we used a pre-trained U-Net model with an average Dice similarity coefficient (DSC) greater than 0.96. First, we extracted the PDF to grade the infection of each lobe and selected five specific thresholds as feature vectors. We then assigned this feature vector to a support vector machine (SVM) model and made the final prediction of the infection severity. Using the T-Test statistics, we calculated the p-value at different pixel thresholds and reported the significant differences in the pixel values. In most cases, the p-value was less than 0.05. Our developed model was developed on roughly labeled data without any manual segmentation, which estimated lung infection involvements with the area under the curve (AUC) in the range of [0.64, 0.87]. The introduced model can be used to generate a systematic automated report for individual patients infected by COVID-19.

Temporomandibular joint (TMJ) disorders as first clinical manifestations in external auditory canal cholesteatoma. A case report.

INTRODUCTION AND IMPORTANCE: Cholesteatoma is a common occurrence in the middle ear, whereas cholesteatoma of the external auditory canal (EAC) is a rare condition. We report an unusual presentation of the cholesteatoma in the EAC. CASE PRESENTATION: We report a case of a 67-year-old male presented to the ENT casualty with a longstanding history of left sided squeaky type sound, aggravated whenever he talks or eats. He subsequently had a Computed Tomography (CT) scan of the left petrous bone which identified a left-sided EAC cholesteatoma. Clinical symptoms of EAC cholesteatoma are non-specific, and hence we recommend considering cholesteatoma when patients present with abnormal EAC symptoms and intact tympanic membrane. CLINICAL DISCUSSION: His cranial nerves examination was normal, and the tympanic membrane was intact. His blood count and infective marker were normal. The CT scan of the brain showed a lesion in the left external auditory canal close to the tympanic membrane. The lesion was in contact with the anterior inferior canal wall which had features suggesting bony erosion. Gas bubble seen in the posterior part of the TMJ was in relation to bony erosion of the EAC. CONCLUSION: The cholesteatoma of the EAC is very rare. CT scan can provide detailed information about the extent of external ear canal cholesteatoma, which can be used to identify complications of the disease, in addition to differentiating the external ear canal from the middle ear cholesteatoma. Early recognition of cholesteatoma and prompt treatment is essential to prevent catastrophic complications.

The effect of traffic noise on cognitive performance with regard to personality traits: A laboratory experiment study.

BACKGROUND: Exposure to traffic noise could play an important part in inducing psychological disorders which in turn can affect individuals' cognitive and mental performance. OBJECTIVE: The aim of this study was to determine the effect of traffic noise exposure on the cognitive performance with regard to subjects' personality traits. METHODS: Sixty students with normal hearing and vision took part in this experimental study. In order to simulate the traffic noise condition of Tehran, the noise from several busy streets was first carefully recorded. Later on, the subjects were exposed to this recorded noise in an anechoic chamber. Also, the NEO-five factor inventory questionnaire and the continuous performance test were used to assess personality traits and cognitive performance of participants respectively. RESULTS: The results showed that the cognitive features of the study, such as reaction time and the number of commission/omission errors in continuous performance testing increased significantly after exposure to the traffic noise (p < 0.05), and among the personality traits, only the neuroticism has a significant correlation with response time in the continuous performance tests (p < 0.05). CONCLUSIONS: Apart from the effect of traffic noise on cognitive function, the findings of this study confirmed that Neuroticism (one of the personality traits) also significantly affect the cognitive performance of individuals when they are exposed to traffic noise in laboratory conditions.

Bioactive Carboxymethyl Starch-Based Hydrogels Decorated with CuO Nanoparticles: Antioxidant and Antimicrobial Properties and Accelerated Wound Healing In Vivo.

In this study, nanocomposite hydrogels composed of sodium carboxymethylated starch (CMS)-containing CuO nanoparticles (CMS@CuO) were synthesized and used as experimental wound healing materials. The hydrogels were fabricated by a solution-casting technique using citric acid as a crosslinking agent. They were characterized by Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA) to evaluate their physicochemical properties. In addition, swelling, antibacterial activities, antioxidant activities, cytotoxicity, and in vivo wound healing were investigated to evaluate the wound healing potential of the CMS@CuO nanocomposite hydrogels. Growth inhibition of the Gram-positive and Gram-negative pathogens, antioxidant activity, and swelling were observed in the CMS@CuO nanocomposite hydrogels containing 2 wt.% and 4 wt.% CuO nanoparticles. The hydrogel containing 2 wt.% CuO nanoparticles displayed low toxicity to human fibroblasts and exhibited good biocompatibility. Wounds created in rats and treated with the CMS@2%CuO nanocomposite hydrogel healed within 13 days, whereas wounds were still present when treated for the same time-period with CMS only. The impact of antibacterial and antioxidant activities on accelerating wound healing could be ascribed to the antibacterial and antioxidant activities of the nanocomposite hydrogel. Incorporation of CuO nanoparticles in the hydrogel improved its antibacterial properties, antioxidant activity, and degree of swelling. The present nanocomposite hydrogel has the potential to be used clinically as a novel wound healing material.

Trans-cutaneous electrical nerve stimulation to treat dry mouth (xerostomia) following radiotherapy for head and neck cancer. A systematic review.

BACKGROUND: A dry mouth or xerostomia is one of the most common long-term complications following radiotherapy for head and neck cancer and has a negative impact on quality of life in cancer survivors. Transcutaneous electrical nerve stimulation (TENS) is a novel approach to improving saliva flow in these patients. OBJECTIVE: To perform a systematic review of studies evaluating TENS in the treatment of radiotherapy induced xerostomia in head and neck cancer patients. DATA COLLECTION AND ANALYSIS: A comprehensive electronic search was performed in PubMed/MEDLINE, the Cochrane Library, and Google Scholar databases for appropriate published studies. The last search was conducted in January 2020. Two review authors assessed all studies identified by the search strategy and carried out data extraction. RESULTS: Five studies were included in the systematic review which analysed a total of 280 patients with head and neck cancer. Methodological quality and outcomes were evaluated in every study included. The outcome measure was either subjectively assessed or objectively measured. Three studies used conventional TENS therapy to stimulate parotid glands which produced a significant increase in saliva production following therapy. Two studies used acupunctured TENS type to electrically stimulate acupuncture points scattered in the body and they reported improvement in saliva production at the same level as medical treatment. No reported adverse effect of TENS was identified. CONCLUSIONS: This systematic review confirms the safety and feasibility of TENS in the treatment of xerostomia. It is established that commencing daily TENS therapy simultaneously with radiotherapy has the most efficacy. Given the nonspecific parameters used in the included studies, further evidence is needed in order to establish optimal settings and parameters of TENS for treatment of xerostomia.

Design and characterization of new antimicrobial peptides derived from aurein 1.2 with enhanced antibacterial activity.

Antimicrobial peptides (AMPs) are promising alternative agents for treating multidrug-resistant bacterial infections. Aurein 1.2 is a natural 13-amino acid AMP with antibacterial activity against Gram-positive bacteria. In this study, we designed three novel AMPs: aurein M1 (A10W), aurein M2 (D4K, E11K), and aurein M3 (A10W, D4K, E11K) to analyze the effect of Trp substitution and enhancement of positive charge on the activity of aurein 1.2. The AMP probability, physicochemical properties, secondary and tertiary structures, and amphipathic structure were predicted by various bioinformatics tools. After the synthesis of the peptides, their antibacterial activity, hemolysis, cytotoxicity, and structural analysis were assayed. Compared to the selectivity of aurein 1.2, the selectivity of aurein M2 and M3 with a net positive charge of +5 was improved 11.30- and 8.00-fold against Gram-positive and -negative bacteria, respectively. The hemolytic activity of aurein M2 was lower than that of aurein 1.2 and M3, while the higher percentage of human fibroblast cells were alive in the presence of aurein M3. Also, the MICs of aurein M3 toward Staphylococcus aureus and Escherichia coli at the physiologic salt were ≤16, which is recommended as a promising candidate for clinical investigation. Circular dichroism analysis indicated an alpha-helical structure in the peptide analogs that is similar to aurein 1.2 in the presence of 10 mM SDS. Therefore, increasing positive charge can be used successfully as an approach for improving the potency and selectivity of AMPs. Moreover, the beneficial effect of Trp substitution depends on its position and the sequence of peptides.