Percutaneous Urine Sampling from Renal Pelvis: A Minimally-Invasive Method to Determine the Origin of Post-Transplant Proteinuria

A 14-year-old boy with end-stage renal disease secondary to focal segmental glomerulosclerosis complicated with heavy proteinuria received a non- related living kidney transplantation. Postoperatively he continued to excrete higher level of proteinuria. Allograft biopsy showed mild mesangial expansion and hypercellularity. Urine sample was collected from allograft renal pelvis under local anesthesia and ultrasound guidance.Based on the importance of heavy proteinuria and lack of definite method of differentiating its source during the early weeks after kidney transplantation, it seems that percutaneous renal pelvis urine sampling may be noted as a preferred method of detecting the source of proteinuria.Keywords: Focal Segmental Glomerulosclerosis; Kidney Transplantation; Ultrasonography; Proteinuria; Allografts

Primary Angle Closure Glaucoma-associated Genetic Polymorphisms in Northeast Iran

Purpose: To evaluate the association of five different polymorphisms from a genomewide- associated study with susceptibility to glaucoma in the northeast Iranian population. Methods: Hundred and thirty patients with primary angle closure glaucoma (PACG) and 130 healthy controls were genotyped for the polymorphic regions with the aid of tetraamplification refractory mutation system-polymerase chain reaction. The association of these variants with the disease susceptibility was measured statistically with the logistic regression method. Results: Hundred and thirty patients with PACG (53 males, 77 females) with a mean age of 64.5 ± 6.2 years and 130 healthy control subjects (51 males, 79 females) with a mean age of 64.0 ± 5.7 years were selected for evaluation. There was a significant association between rs3816415 (P = 0.005), rs736893 (P < 0.001), rs7494379 (P < 0.001), and rs1258267 (P = 0.02) with PACG susceptibility. This association could not be shown for rs3739821. Conclusion: It was revealed that studied variants in GLIS3, EPDR1, FERMT2, and CHAT genes can contribute to the incidence of PACG. Additional studies in other populations are needed to evaluate DPM2-FAM102A

Protective Effect of Ghrelin on Oxidative Stress and Tissue Damages of Mice Testes Followed by Chemotherapy With Cyclophosphamide

Objectives: Cyclophosphamide (CP) is one of the common medications used as chemotherapy and immune-suppressive agent in organ transplantation. Despite numerous clinical applications of this drug in cancer treatment, it causes adverse effects on body tissues, especially the male reproductive organs by increasing oxidative stress. The present study aimed to analyze the effects of ghrelin, as an antioxidant substance, on testicular damages induced by CP. Materials and Methods: Forty male mice were randomly divided into 4 groups: 1) control; 2) CP; 3) CP + ghrelin; and 4) ghrelin. CP (100 mg/kg body weight) was injected intraperitoneally once a week and ghrelin (80 μg/kg body weight) was administered daily for 5 weeks. After 5 weeks, the testicles were removed and we investigated histological changes and testicular oxidative stress markers including malondialdehyde, superoxide dismutase, glutathione peroxidase, and total antioxidant capacity. Results: Our results showed that CP increased malondialdehyde level and decreased glutathione peroxidase, superoxide dismutase, and the total antioxidant capacity (P < 0.05). Furthermore, degenerative changes in the testicular tissue were observed in CP group. The aforementioned factors were improved in the group that was treated with ghrelin (P < 0.05). Conclusions: The results of this study revealed that ghrelin decreases the damages caused by CP in testicular tissue of mice by reducing lipid peroxidation and increasing total antioxidant capacity

Myopic regression after photorefractive keratectomy: a retrospective cohort study

Background: Myopic regression is a major complication of photorefractive keratectomy (PRK). The rates and causes vary considerably among different studies. This study aimed to investigate myopic regression at six months after myopic PRK. Methods: In this retrospective cohort study, we included all eligible patients with myopia ranging from - 0.75 to - 9 D, aged 18 to 50 years, who underwent PRK by a single surgeon with the availability of preoperative and postoperative data at six months after the initial procedure. All participants underwent comprehensive ophthalmic examinations preoperatively and at six months post-PRK. Overcorrection was planned based on the participant’s age range to achieve the desired refractive result after PRK. All patients received the same postoperative antibiotic and steroid eye drops in a similar dosage regimen, and the contact lenses were removed after complete corneal epithelial healing. Based on the spherical equivalent of refraction six months after PRK, eyes without and with myopic regression were allocated into groups 1 and 2, respectively. Results: We included 254 eyes of 132 patients who underwent myopic PRK with a mean (standard deviation) age of 30.12 (7.48) years; 82 (62.12%) were women and 50 (37.88%) were men. The frequency of myopic regression was significantly lower in patients with younger age, lower preoperative cylindrical refraction, and lower ablation depth (all P &lt; 0.05). Overcorrection was more successful in eyes with low myopia than in eyes with high myopia (P &lt; 0.05). The highest frequency of myopic regression occurred in eyes with moderate myopia (25.68%), followed by eyes with high myopia (20.0%) and low myopia (6.54%). Among different age groups, patients aged less than or equal to 30 years had a lower frequency of myopic regression. The frequency of myopic regression in the different age groups was 5.0% at 18-20 years, 7.46% at 26-30 years, 12.28% at 21-25 years, 21.31% at 31-35 years, and 26.53% at 36-50 years. Conclusions: Overcorrection was more successful in eyes with low myopia than in eyes with high myopia. The success rate was higher in younger patients with lower astigmatism and ablation depths. Myopic regression was most frequent in eyes with moderate myopia, followed by those with high and low myopia. Further studies should replicate our findings over a longer follow-up period with a larger sample size before generalization is warranted

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis

Pharmacological effects of Safranal: An updated review

Safranal (a monoterpene aldehyde) is the major volatile component of saffron which is responsible for the saffron unique odor. Several studies have shown the pharmacological activities of safranal including anti-oxidant, anti-inflammatory, cardioprotective, neuroprotective, nephroprotective, gastrointestinal protective, etc.  This study was designed to review the pharmacological and medical effects of safranal and up-to-date previous knowledge. Moreover, some patents related to the pharmacological effects of safranal were gathered. Therefore, electronic databases including Web of Sciences, Scopus, and Pubmed for pharmacological effects and US patent, Patentscope, and Google Patent for patents were comprehensively searched by related English keywords from 2010 to June 2022. According to our review, most of the studies are related to the safranal effects on CNS such as antianxiety, analgesic, anticonvulsant, antiischemic, anti-tremor, memory enhancement and its protective effects on neurodegenerative disorders such as Alzheimer’s, Parkinson and Huntington diseases. Other effects of safranal are antiasthmatic, antihypertensive, antiaging, anticataract, etc. Moreover, the protective effects of this agent on metabolic syndrome and diabetic nephropathy have been shown. Different mechanisms including anti-oxidant, anti-inflammatory, muscle relaxation, antiapoptotic, and regulatory effects on the genes and proteins expression related to signaling pathways of oxidative stress, inflammation, apoptosis, proliferation, etc. are involved in safranal pharmacological effects. Some patents for the prevention and/or treatment of different diseases such as liver cancer, sleep disorder, depression,  cognitive disorder, obesity and PMS were also included. Based on the documents, safranal is considered a promising therapeutic agent although more clinical studies are needed to verify the beneficial effects of safranal in humans

The Larval Stages of Echinostoma spp. in Freshwater Snails as the First and Second Intermediate Hosts in Gilan and Mazandaran Provinces, Northern Iran

Background: Identification of the larval stages of Echinostoma spp. in freshwater snails is an essential guide to continue monitoring the possibility of their transmission and the potential of echinostomiasis in areas where trematodes are the primary agent of parasitic diseases. The aim of this study was investigate Echinostoma using morphological and molecular techniques.Methods: The study was conducted in Gilan and Mazandaran Provinces, northern Iran, from April 2019 to October 2021. Overall, 5300 freshwater snails were randomly collected and were identified using external shell morphology. Meanwhile, snails infected with trematodes were studied via shedding and dissecting methods. Larvae stages of Echinostoma were identified and the genomic DNA of the samples was extracted. The PCR amplification of the ITSI gene was carried out for 17 isolates and products were sequenced. Seven sequences were deposited in GenBank.Results: Totally, 3.5% of snails containing three species (Stagnicola sp., Radix sp. and Planorbis sp.) were infected with two types of cercaria, E. revolutum with 37 and Echinostoma sp. with 45 spines in the collar. Moreover, 35% of the snails were infected with Echinostoma spp. metacercaria. Phylogenetic analysis illustrated that isolates were included in two ITSI haplogroups. Conclusion: Results showed the potential hazard of a zoonotic parasite as Echinostoma in northern Iran. The potential of disease environmental relationship investigation and resource control optimization is necessary for effective disease prevention and health management

MultiNotch MS3 Enables Accurate, Sensitive, and Multiplexed Detection of Differential Expression across Cancer Cell Line Proteomes

Multiplexed quantitation via isobaric chemical tags (e.g., tandem mass tags (TMT) and isobaric tags for relative and absolute quantitation (iTRAQ)) has the potential to revolutionize quantitative proteomics. However, until recently the utility of these tags was questionable due to reporter ion ratio distortion resulting from fragmentation of coisolated interfering species. These interfering signals can be negated through additional gas-phase manipulations (e.g., MS/MS/MS (MS3) and proton-transfer reactions (PTR)). These methods, however, have a significant sensitivity penalty. Using isolation waveforms with multiple frequency notches (i.e., synchronous precursor selection, SPS), we coisolated and cofragmented multiple MS2 fragment ions, thereby increasing the number of reporter ions in the MS3 spectrum 10-fold over the standard MS3 method (i.e., MultiNotch MS3). By increasing the reporter ion signals, this method improves the dynamic range of reporter ion quantitation, reduces reporter ion signal variance, and ultimately produces more high-quality quantitative measurements. To demonstrate utility, we analyzed biological triplicates of eight colon cancer cell lines using the MultiNotch MS3 method. Across all the replicates we quantified 8 378 proteins in union and 6 168 proteins in common. Taking into account that each of these quantified proteins contains eight distinct cell-line measurements, this data set encompasses 174 704 quantitative ratios each measured in triplicate across the biological replicates. Herein, we demonstrate that the MultiNotch MS3 method uniquely combines multiplexing capacity with quantitative sensitivity and accuracy, drastically increasing the informational value obtainable from proteomic experiments

Author Correction: Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper