Bacteriophages and bacterial extracellular vesicles, threat or opportunity?

Emergence of antimicrobial-resistant bacteria (AMR) is one of the health major problems worldwide. The scientists are looking for a novel method to treat infectious diseases. Phage therapy is considered a suitable approach for treating infectious diseases. However, there are different challenges in this way. Some biological aspects can probably influence on therapeutic results and further investigations are necessary to reach a successful phage therapy. Bacteriophage activity can influence by bacterial defense system. Bacterial extracellular vesicles (BEVs) are one of the bacterial defense mechanisms which can modify the results of bacteriophage activity. BEVs have the significant roles in the gene transferring, invasion, escape, and spreading of bacteriophages. In this review, the defense mechanisms of bacteria against bacteriophages, especially BEVs secretion, the hidden linkage of BEVs and bacteriophages, and its possible consequences on the bacteriophage activity as well phage therapy will be discussed.

A simplified method of bacteriophage preparation for transmission electron microscope.

Bacteriophages are viruses that infect bacteria. Researchers use different methods to study the characteristics of bacteriophages. Transmission electron microscope (TEM) is considered the best method to analyze these characteristics. However, the quality of TEM micrographs is significantly influenced by the preparation methods used to prepare the bacteriophages sample. In this study, researchers compared two different methods for preparing the bacteriophage samples. In one method was used SM buffer, while in the other used deionized water. The results were analyzed by TEM and compared with each other. Additionally, the viability of bacteriophage in deionized water and SM buffer at 4°C was determined through plaque assay within 72 hours. TEM micrographs showed that the quality of bacteriophage sample prepared with deionized water is superior to those prepared with SM buffer. Furthermore, the titer of the bacteriophages did not show a significant reduction during 72 hours in both SM and deionized water. In conclusion, the results suggested that preparation method can significantly impact the quality of TEM micrographs. Using sterile deionized water for the preparation of bacteriophages is a simple way to improve the quality of TEM micrographs and it is advisable to send the samples to the laboratory within 72 hours.

Investigation on microbial deterioration of exquisite collection of old manuscripts in Iran.

Background and Objectives: The present study was to evaluate the microbial diversity inhabiting biodeteriorated precious manuscripts of the Holy Quran placed in one of the repositories of the Library of Astan Quds Razavi (AQR), and its relation to the air microbial diversity. Materials and Methods: Three non-invasive sampling methods, culture-based techniques, and molecular identification were used to investigate the microorganisms involved in deterioration. To investigate the air microbial quality and its role in the destruction of the repository objects, air samples were taken from six different points inside the repository. Biomodeling studies were designed to verify the impact of microbial isolates. Results: 14 fungal isolates were obtained from three deteriorated ancient Quran manuscripts. The most frequently isolated fungi from the different substrates were Aspergillus spp. and Penicillium spp. In the air, the prevalence across fungal genera was rather uniform. 30 species of the identified bacteria were collected from three manuscripts. The results obtained in the present study showed that the bacterial species from different genera belonged to three phyla: Proteobacteria (n = 2), Actinobacteria (n = 4), and Firmicutes (n = 24). The paper strips were artificially colonized by Aspergillus sp., Penicillium chrysogenum, and Talaromyces diversus producing spots which were visible to the naked eye. In the scanning electron microscopy images, the colonization of the selected organism was observed. Conclusion: The characteristics of paper inoculated artificially with these microbial isolates confirmed their deteriorating effects. Based on molecular identification, the similarity of fungal and bacterial species isolated from both substrates and air samples suggest the direct relationship between microorganisms from the air and those isolated from the manuscripts.

Comparison of culture and PCR-DGGE methods to evaluate the airways of cystic fibrosis patients and determination of their antibiotic resistance profile.

Background and Objectives: Respiratory infections are the most serious condition in cystic fibrosis (CF) patients; therefore, a thorough comprehension of the diversity and dominant microbial species in CF airways has a crucial role in treatment. Our objective was to determine the antibiotic resistance profile of CF airways microbiota and compare culture methods and PCR-DGGE to evaluate bacterial diversity. Materials and Methods: Pharyngeal swabs from 121 CF patients were collected. The samples were then cultured, identified and antibiotic resistance testing was performed. Thirty samples were subjected to further molecular surveys. DNA contents of these samples were extracted and amplified using nested-PCR technique and their bacterial diversity was assessed by DGGE. The DGGE patterns were visualized and certain bands were excised and purified. Next, the DNA was amplified by another round of PCR and sent out for sequencing. Results: Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most prevalent species isolated using culture methods. S. aureus was the most common bacteria among 6 years and younger patients; while, P. aeruginosa had more prevalence among older ones. The PCR-DGGE results showed more diversity than culture methods, particularly in younger patients who exhibited more bacterial diversity than the older groups. Sequencing results unveiled the presence of certain bacterial species including Haemophilus parainfluenzae and Stenotrophomonas maltophilia which were completely missed in culture. Conclusion: Even though culture-dependent methods are cost-effective, PCR-DGGE appeared to be more efficient to determine bacterial diversity. PCR-DGGE detects less abundant species, though their viability could not be determined using this method.

A new nanobiotic: synthesis and characterization of an albumin nanoparticle with intrinsic antibiotic activity.

Background and Objectives: With entering the "post-antibiotic era", antibiotic resistance is one of the most important problems in food security, health and medicine. Invention of nanoparticles with intrinsic antimicrobial activity has been provided a new tool to combat the problem, including some metal nanoparticles. But protein nanoparticles have been often used as nano-carrier for antibiotic drugs, not for their own antibiotic activity. In this article we have fabricated a very small BSA-NP without any chemical modification on BSA molecules showing antibacterial activity. Materials and Methods: Bovine serum albumin nanoparticle (BSA-NP) was synthesized using botton-up approach, by dissolution of BSA in urea-containing Tris buffer for 60 min at 60°C. Then, the BSA solution was dialyzed against distilled water in order to nanoparticle formation. The resulted BSA-NP has been characterized by dynamic light scattering (DLS), field emission surface electron microscopy (FESEM), SDS-PAGE, Fourier transform infrared spectroscopy (FTIR) and UV-spectrophotometery. Minimum inhibitory concentration (MIC) method was used for evaluation of antibacterial activity of BSA-NP against Staphylococcus aureus and Pseudomonas aeruginosa. Results: The results obtained by DLS technique indicated that BSA molecules were self-assembled into small aggregates with a hydrodynamic diameter of 23.23 ± 2.1 nm. With a small polydispersity index (PDI=0.522), the nanoparticles had good spherical uniformity. The nanoparticles made from a single type of protein molecule (BSA) and have a relatively transparent appearance. The BSA-NPs caused a decrease in cell growth of both P. aeruginosa and S. aureus. Moreover, they had a bacteriostatic effect on P. aeruginosa (MIC=112×10-5 µM). Conclusion: In this study, using a green synthesis method, we succeeded in synthesizing a very small uniform BSA nanoparticles without any chemical modification on BSA molecules. It also has bacteriostatic properties against P. aeruginosa. Therefore, it is hypothesized that our BSA-NPs may be effective as a new approach to combat antibiotic resistance.

Interplay of valley polarized dark trion and dark exciton-polaron in monolayer WSe2.

The interactions between charges and excitons involve complex many-body interactions at high densities. The exciton-polaron model has been adopted to understand the Fermi sea screening of charged excitons in monolayer transition metal dichalcogenides. The results provide good agreement with absorption measurements, which are dominated by dilute bright exciton responses. Here we investigate the Fermi sea dressing of spin-forbidden dark excitons in monolayer WSe2. With a Zeeman field, the valley-polarized dark excitons show distinct p-doping dependence in photoluminescence when the carriers reach a critical density. This density can be interpreted as the onset of strongly modified Fermi sea interactions and shifts with increasing exciton density. Through valley-selective excitation and dynamics measurements, we also infer an intervalley coupling between the dark trions and exciton-polarons mediated by the many-body interactions. Our results reveal the evolution of Fermi sea screening with increasing exciton density and the impacts of polaron-polaron interactions, which lay the foundation for understanding electronic correlations and many-body interactions in 2D systems.

Chlamydia pneumonia infection and risk of multiple sclerosis: A meta-analysis.

BACKGROUND: The role of infectious agents, including Chlamydia pneumoniae (Cpn), in the development of multiple sclerosis (MS), is still a matter of major contention. OBJECTIVE: This meta-analysis study aimed to assess the actual involvement of Cpn in MS development. METHODS: We undertook a search of international scientific databases to identify eligible studies. We used a random-effects meta-analysis model (REM) to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity was calculated using the I2 statistic. Sensitivity and subgroup analyses were applied to assess the effects of study characteristics and socio-demographic variables on the pooled OR. RESULTS: We identified 37 studies comprising 51 datasets that satisfied the inclusion criteria. Considering diagnostic methods for Cpn, 26 and 25 datasets used PCR- and serological-based methods, respectively. In PCR-based datasets, REM showed a significant positive association between Cpn infection and the development of MS (OR, 5.29; 95% CI, 3.12-8.97), while a non-significant positive association was achieved in serological-based datasets (OR, 1.34; 95% CI, 0.88-2.03). In subgroup analyses on PCR-based datasets, results were significant for both CSF (OR, 5.70) and serum (OR, 4.84) samples; both healthy (OR, 16.11) and hospital-based (OR, 2.88) controls; and both moderate (OR, 5.14) and high (OR, 5.48) quality studies. In serological-based datasets, only those that used CSF samples yielded significant results (OR, 3.41). CONCLUSIONS: Our findings verify the significant positive relationship between Cpn infection and MS. We advocate prospective cohort studies with lifelong follow-ups and also experimental studies to better understand the role of Cpn in MS development.

Optimization and synthesis of a novel sorbent composite based on magnetic chitosan-amine-functionalized bimetallic MOF for the simultaneous dispersive solid-phase microextraction of four aflatoxins in real water, herbal distillate, and food samples.

Aflatoxins (AFs), an important category of pollutants, are formed in many foods and adversely affect human health. Therefore, their determination is critical to ensuring human food health. An efficient dispersive solid-phase microextraction technique was developed as a simple and straightforward sample preparation technique for determination of four aflatoxins using a high-performance liquid chromatography (HPLC) fluorescence detector. A novel efficient, green sorbent for extracting AFs was synthesized based on hydrothermal and chemical strategies. The amounts of three sorbent components were optimized using a mixture design (simplex lattice design), including 14 experiments. The optimal amount of amino-bimetallic Fe/Ni-MIL-53 nanospheres, chitosan, and magnetic Fe3O4 nanoparticles as sorbent components was 0.87, 0.67, and 0.47 g, respectively. Also, various factors affecting the process of AF determination were studied and optimized in two successive experimental designs, including the definitive screening design and the Box-Behnken design. Under optimal conditions, the linear ranges for measuring aflatoxin B1, aflatoxin B2, aflatoxin G1, and aflatoxin G2 were 0.05-82.6, 0.07-86.4, 0.08-85.7, and 0.07-89.5 ng mL-1, respectively. The relative standard deviations under inter-day and intra-day conditions for measuring AFs at three analyte concentrations were determined in triplicate analysis and were in the ranges of 3.7-4.6% and 4.9-6.1% for water sample analysis, respectively. The qualitative detection limits for determining AFs were between 0.01 and 0.05 ng mL-1. The pre-concentration factor of the method for measuring AFs ranged from 739.7 to 802.1. The proposed method was used for determining AFs in several real samples, including herbal distillate, black tea, corn, and real water samples. The relative recovery and standard deviation were 87.8-97.8% and 4.10-6.82%, respectively.

Ofatumumab regimens in chronic lymphocytic leukemia: a meta-analysis.

Ofatumumab's therapeutic impact on patients with chronic lymphocytic leukemia (CLL) has been the subject of increasing clinical research. However, in recent years, no studies have yet provided a pooled assessment of the treatment effect of ofatumumab vs. non-ofatumumab regimens. Therefore, we conducted a progression meta-analysis to evaluate the efficacy of ofatumumab-based treatment in CLL patients using data from clinical studies. Relevant publications from PubMed, Web of Science and ClinicalTrials.gov were searched. The efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The articles reviewed in the mentioned databases and matching the specified keywords were searched until January 2023. The pooled efficacy analysis showed that there was a significant difference in PFS [hazard ratios (HR) = 0.62, 95% confidence interval (CI) = 0.52-0.74] and no significant difference in OS (HR = 0.86, 95% CI = 0.71-1.03) between ofatumumab-based therapy and non-ofatumumab therapy. Our analysis showed the pooled efficacy for PFS was statistically significantly improved with ofatumumab-based treatments for CLL compared with other groups. Also, ofatumumab had no statistically significant improvement in the OS of patients with CLL. Thus, ofatumumab-based therapies for CLL patients could be improved by other combinational-based regimens.

Evaluation of SARS-CoV-2 RNA Presence in Treated and Untreated Hospital Sewage.

Wastewater-based epidemiology (WBE) is a potential approach for determining the viral prevalence in a community. In the wake of the COVID-19 pandemic, researchers have begun to pay close attention to the presence of SARS-COV-2 RNA in various wastewaters. The potential for detecting SARS-CoV-2 RNA in hospital sewage could make it an invaluable resource for epidemiological studies. In this regard, two specialized hospitals dedicated to COVID-19 patients were chosen for this investigation. Both hospitals utilize the same wastewater treatment systems. The influent and effluents of the two hospitals were sampled in May and June of 2021, and the samples were evaluated for their chemical properties. According to the findings of this study, the wastewater qualities of the two studied hospitals were within the standard ranges. The sewage samples were concentrated using ultrafiltration and PEG precipitation techniques. The E and S genes were studied with RT-qPCR commercial kits. We found E gene of SARS-CoV-2 in 83.3% (5/6) and 66.6% (4/6) of wastewater samples from hospital 1 and hospital 2, respectively, using ultrafiltration concentration method. Wastewater samples taken after chlorine treatment accounted for 16.6% of all positive results. In addition, due to the small sample size, there was no significant correlation (p > 0.05) between the presence of SARS-CoV-2 in wastewater and the number of COVID-19 cases. Hospitals may be a source of SARS-CoV-2 pollution, thus it is important to monitor and enhance wastewater treatment systems to prevent the spread of the virus and safeguard the surrounding environment.

Autophagy: A challengeable paradox in cancer treatment.

OBJECTIVE: Autophagy is an intracellular degradation pathway conserved in all eukaryotes from yeast to humans. This process plays a quality-control role by destroying harmful cellular components under normal conditions, maintaining cell survival, and establishing cellular adaptation under stressful conditions. Hence, there are various studies indicating dysfunctional autophagy as a factor involved in the development and progression of various human diseases, including cancer. In addition, the importance of autophagy in the development of cancer has been highlighted by paradoxical roles, as a cytoprotective and cytotoxic mechanism. Despite extensive research in the field of cancer, there are many questions and challenges about the roles and effects suggested for autophagy in cancer treatment. The aim of this study was to provide an overview of the paradoxical roles of autophagy in different tumors and related cancer treatment options. METHODS: In this study, to find articles, a search was made in PubMed and Google scholar databases with the keywords Autophagy, Autophagy in Cancer Management, and Drug Design. RESULTS: According to the investigation, some studies suggest that several advanced cancers are dependent on autophagy for cell survival, so when cancer cells are exposed to therapy, autophagy is induced and suppresses the anti-cancer effects of therapeutic agents and also results in cell resistance. However, enhanced autophagy from using anti-cancer drugs causes autophagy-mediated cell death in several cancers. Because autophagy also plays roles in both tumor suppression and promotion further research is needed to determine the precise mechanism of this process in cancer treatment. CONCLUSION: We concluded in this article, autophagy manipulation may either promote or hinder the growth and development of cancer according to the origin of the cancer cells, the type of cancer, and the behavior of the cancer cells exposed to treatment. Thus, before starting treatment it is necessary to determine the basal levels of autophagy in various cancers.

Developments of Microextraction (Extraction) Procedures for Sample Preparation of Antidepressants in Biological and Water Samples, a Review.

Antidepressants are an important class of drugs to treat various types of depression. The determination of antidepressants is crucial in biological samples to control adverse effects in humans and study pharmacokinetics and bioavailability. Direct measurement of antidepressants in biological and water samples is a considerable challenge for analysts due to their low concentration, the high matrix effects of real samples, and the presence of metabolites of these drugs in biological samples. The challenge leads to using sample preparation processes as a critical step in determining antidepressants. Extraction and microextraction procedures have been widely utilized as sample preparation procedures for these drugs. The purposes of extraction or microextraction methods for antidepressant medications are to preconcentrate the analyte, reduce the matrix effects, increase the selectivity of the procedures, and convert the sample to a suitable format for introducing it into detection systems. In the review, the various extraction and microextraction methods of these drugs in biological, real water, and wastewater samples were investigated. The theory of each technique was briefly addressed to understand the features and factors affecting each method. The extraction and microextraction methods were classified based on their application for antidepressants, and the advantages and disadvantages of each technique were reviewed. The new developments to overcome the limitations of each procedure were discussed. The investigation indicated the number of applications of liquid-phase microextraction for extracting antidepressants has been almost equal to that of solid-phase microextraction.

Wound healing promotion by flaxseed extract-loaded polyvinyl alcohol/chitosan nanofibrous scaffolds.

Impaired wound healing is a severe complication of sufferers, related to prolonged wound closure, a high infection rate, and eventually disabilities of organs. To aid resolve this issue, we developed the electrospun polyvinyl alcohol and chitosan (PVA/CS) nanofibrous scaffold-loaded flaxseed extract. The scaffold containing 10 wt% of the extract indicated a three-dimensional cross-network with a nano-scale diameter (257 ± 37 nm) and smooth surface. Also, the relevant analyses confirmed high water absorption, porosity, and wettability of the scaffold. Fourier-transform infrared (FTIR), degradation, and mechanical studies revealed the intact presence and loading of the extract into the scaffold, the complete degradation over 48 h, and a high tensile elastic modulus. Besides, the advanced scaffold displayed remarkable anti-oxidant and could inhibit the growth of both Gram-positive and negative bacteria compared to the free PVA/CS scaffold. Desired fibroblast viability and blood compatibility of flaxseed-loaded scaffold endorsed the biocompatibility for wound zones. The in vitro studies showed that the flaxseed-loaded scaffold resulted in an accelerated wound healing process and 100 % closure of the scratched area within 48 h. The results obtained reveal that the flaxseed-loaded PVA/CS electrospun scaffold could be effectively applied for wound healing promotion.

Increased expression of androgen receptor and PSA genes in LNCaP (prostate cancer) cell line due to high concentrations of EGCG, an active ingredient in green tea.

OBJECTIVES: Androgen receptor (AR) play a key role in the onset and progression of prostate cancer. Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound and the active ingredient in green tea, which is involved in modulating gene expression through epigenetic alterations. Previous studies have shown that EGCG at low concentrations reduces the expression of AR and prostate-specific antigen (PSA) in the LNCaP cell line of prostate cancer. In this study, the effect of higher EGCG concentrations on AR and PSA expression in LNCaP prostate cancer cell line was investigated. METHODS: In this study, LNCaP prostate cancer cell line was used and after MTT test, concentrations of 40, 60 and 80 µg/mL EGCG were used for treatment. Then, the expression of AR and PSA genes was evaluated by RT-PCR. AR protein expression was also assessed by Western blotting. RESULTS: The present study showed that treatment of LNCaPs cells by EGCG reduces cell proliferation. The IC50 value was 42.7 µg/mL under experimental conditions. It was also observed that EGCG at concentrations of 40 and 80 µg/mL increased the expression of AR and PSA (p<0.05). CONCLUSIONS: The present study showed that the effect of EGCG on AR expression was different at different concentrations, so that unlike previous studies, higher concentrations of EGCG (80 and 40 µg/mL) increased AR and PSA expression. It seems that due to the toxic effects of EGCG in high concentrations on cancer cells and the possibility of its effect on normal cells, more caution should be exercised in its use.

Capsulectomy Shunt Revision versus Repeat Shunt Implantation Following Ahmed Glaucoma Valve Failure in Refractory Glaucoma.

PURPOSE: To investigate the efficacy of capsulectomy shunt revision (CSR) compared with the implantation of a second Ahmed glaucoma valve (re-AGV) in glaucoma patients with failed shunts. DESIGN: Quasi-experimental study. SUBJECTS: Forty-six eyes with failed Ahmed glaucoma valves (AGVs) were included in the study; 25 underwent CSR, whereas 21 underwent re-AGV. METHODS: Patients were scheduled for CSR or re-AGV based on the appearance and accessibility of the existing AGV versus the feasibility for re-AGV in other quadrants. The CSR involved incision and dissection down to the thick fibrous capsule around the AGV plate, which was excised extensively. For re-AGV, the second shunt was implanted in the supranasal or infranasal quadrants. MAIN OUTCOME MEASURES: Surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, IOP reduction ≥ 20% from baseline, and no reoperation for glaucoma. Secondary outcome measures were IOP, number of glaucoma medications, and complications during a 12-month follow-up period. RESULTS: Mean IOP was significantly lower than preoperative values at all time points in both study groups (P < 0.001). Intraocular pressure decreased significantly from 28.3 ± 5.04 mmHg at baseline to 16.4 ± 2.4 mmHg at final follow-up in the capsulectomy group (P = 0.002). Corresponding IOP values for re-AGV were 30.99 ± 6.2 and 13.6 ± 3.8 mmHg, respectively (P = 0.001). Intraocular pressure in the CSR group was higher than re-AGV during the study (P = 0.003). The cumulative probability of success at 12 months was significantly higher in the re-AGV group (87.5% vs 53.3%, P = 0.002). There was no significant difference in the number of glaucoma medications and overall complications rate between the study groups. Wound leakage was the only complication more common in the CSR group (P = 0.012). CONCLUSION: In the eyes with a failed AGV, re-AGV and CSR are both effective. Implantation of a second shunt seems more effective than the surgical revision of an existing device; however, the latter procedure may be a viable option in selected cases. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Determination of serum alkaline phosphatase reference in healthy children aged 1-18 years.

Background: The growth and development of children affect biochemical variables. This population-based study was designed to evaluate the reference interval for alkaline phosphatase (ALP) routinely measured in the clinical laboratory. Methods: For this examination, 873 cases were selected among the healthy children and adolescents aged 1-18 years who referred to the endocrinology clinic of Amirkola Children's Hospital for growth evaluation. After overnight fasting, early morning blood samples were obtained to measure the ALP level and other biochemical parameters using an automatic biochemical analyzer. Subjects were categorized by age, sex, and body mass index (BMI) values. The age groups were categorized as follows: 1-4 years, 5-8 years, 9-13 years, and 14-18 years. Results: There was a significant difference among the age and sex categories; on the contrary, there was no meaningful variation between the two groups categorized by BMI. The reference range for ALP was 474.14-517.71 U/L for children aged 1-4 years, 273.47-871.44 U/L for 5-8 years, 215.04-893.69 U/L for 9-13 years, and 228.9-739.22 U/L for 14-18 years. Also, significant positive correlation was found between ALP with length (P=0.000, r=0.134), weight (=0.04, r=0.073), phosphorus (P) (P=0.001, r=0.122), and alanine aminotransferase (SGPT) (P=0.000, r=0.142) respectively. Conclusion: This project's data established a reference interval for ALP in healthy children and adolescents, which will prepare a basis for diagnosis and monitoring liver- or bone-related disorders.

Superficial Retinal Microvasculature and Choriocapillaris Alterations after Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

Purpose: To compare superficial retinal vascular, choriocapillaris (CC), and choroidal thickness changes in chronic central serous chorioretinopathy (CSCR) patients after half-dose photodynamic therapy (PDT). Method: In this prospective interventional case series study, fifteen eyes of 14 patients with chronic CSCR undergoing half-dose PDT treatment were enrolled. All patients underwent enhanced depth imaging optical coherence tomography angiography (EDI-OCT) and optical coherence tomography angiography (OCTA) at baseline and 3 months after treatment. Best-corrected visual acuity (BCVA), superficial retinal vascular density, CC vessel density, foveal avascular zone (FAZ), central macular thickness (CMT), and choroidal thickness were compared. Results: Mean BCVA before and after PDT was 0.34 ± 0.26 and 0.19 ± 0.25 logMAR, respectively (p=0.011). Mean FAZ before treatment was 410.21 ± 117.00 µm2, which increased to 433.50 ± 116.76 µm2 (P=0.253). Mean vessel density at superficial capillary plexus (SCP) was 38.93 ± 11.12 at baseline, which increased to 39.04 ± 11.43 (P=0.886). Mean CC vessel density was 53.21 ± 4.14 at baseline, which significantly decreased to 51.85 ± 4.21 (P=<0.001). BCVA has no significant correlation with FAZ (P=0.282) and vessel density (P=0.0.241) at SCP. CMT significantly decreased from 380.87 ± 41.66 µ at baseline to 268.20 ± 28.07 µ at 3 months (P=0.132). We did not find any correlation between CMT and FAZ (P=0.040) and vessel density (P=0.686) at SCP. Mean subfoveal choroidal thickness reduced from 411 ± 171 µm before treatment to 372 ± 117 µm (P=0.106). Conclusion: PDT treatment can affect retinal and choroidal structural parameters, but we could not find any significant influence on retinal vascular parameters, including FAZ area and vessel densityonly mean CC vessel density and subfoveal choroidal thickness decreased.

Targeting endothelial cell metabolism in cancerous microenvironment: a new approach for anti-angiogenic therapy.

Anti-angiogenic therapy is a practical approach to managing diseases with increased angiogenesis, such as cancer, maculopathies, and retinopathies. Considering the fundamental gaps in the knowledge of the vital pathways involved in angiogenesis and its inhibition and the insufficient efficiency of existing angiogenesis inhibitors, there is an increasing focus on the emergence of new therapeutic strategies aimed at inhibiting pathological angiogenesis. Angiogenesis is forming a new vascular network from existing vessels; endothelial cells (ECs), vascular lining cells, are the main actors of angiogenesis in physiological or pathological conditions. Switching from a quiescent state to a highly migratory and proliferative state during new vessel formation called "angiogenic switch" is driven by a "metabolic switch" in ECs, angiogenic growth factors, and other signals. As the characteristics of ECs change by altering the surrounding environment, they appear to have a different metabolism in a tumor microenvironment (TME). Therefore, pathological angiogenesis can be inhibited by targeting metabolic pathways. In the current review, we aim to discuss the EC metabolic pathways under normal and TME conditions to verify the suitability of targeting them with novel therapies.

Characterization of plant growth-promoting rhizobacteria (PGPR) in Persian walnut associated with drought stress tolerance.

There is a lack of information on the rhizosphere of nut-bearing trees where microbial populations can benefit roots and tree growth. The current research aimed at discovering plant growth-promoting rhizobacteria (PGPR) in the rhizosphere of soil samples from around the root zone of six walnut trees, each of which was considered as a genotype, i.e. 'TT1', 'TT2', 'SS2', 'ZM1', 'Chandler' and 'Haward'. The trees grew in different arid and semiarid regions of Iran and Turkey. The strains were isolated and identified based on different morphological and biochemical markers. Drought-stress tolerance was assessed in the case of each isolate through their transfer to culture medium, containing polyethylene glycol (PEG6000) at 0 and 373.80 g L-1. Resilient strains were analyzed for measuring their ability to produce siderophore, hydrogen cyanide (HCN), Indole-3-acetic acid (IAA) and Gibberellic acid (GA3). In sum, 211 isolates were identified, of which a large number belonged to the Bacillus genus and, specifically, 78% of the strains were able to grow under drought stress conditions. The genus Arthrobacter was only detected in the rhizosphere of 'ZM1', 'Haward' and 'TT1' genotypes. In 4% of the strains, IAA production exceeded 53 mg L-1, while a high level of phosphorus solubility was verified in 6% of the strains. No strain was found to have the capability of producing HCN. The strains were screened for drought-tolerance, which resulted in the discovery of two promising strains, i.e. ZM39 and Cha43. Based on molecular identification through amplification and sequencing of the 16S rDNA gene, these two strains seemed to belong to Bacillus velezensis and Bacillus amyloliquefaciens, respectively. The discovery of new PGPR strains could probably assist walnut trees in improving their mechanisms of adaptation to drought stress.

Insights from cyanobacterial genomic and transcriptomic analyses into adaptation strategies in terrestrial environments.

Phylogenomic analysis of Nostocsp. MG11, a terrestrial cyanobacterium, and some terrestrial and freshwater Nostoc strains showed that the terrestrial strains grouped together in a distinctive clade, which reveals the effect of habitat on shaping Nostoc genomes. Terrestrial strains showed larger genomes and had higher predicted CDS contents than freshwater strains. Comparative genomic analysis demonstrated that genome expansion in the terrestrial Nostoc is supported by an increase in copy number of the core genes and acquisition of shared genes. Transcriptomic profiling analysis under desiccation stress revealed that Nostoc sp. MG11 protected its cell by induction of catalase, proteases, sucrose synthase, trehalose biosynthesis and maltodextrin utilization genes and maintained its normal metabolism during this condition by up-regulation of genes related to phycobilisomes and light reactions of photosynthesis, CO2 fixation and protein metabolism. These results provide insights into the strategies related to survival and adaptation of Nostoc strains to terrestrial environments.