EGFR- and Integrin αVß3-Targeting Peptides as Potential Radiometal-Labeled Radiopharmaceuticals for Cancer Theranostics.

The burgeoning field of cancer theranostics has witnessed advancements through the development of targeted molecular agents, particularly peptides. These agents exploit the overexpression or mutations of specific receptors, such as the Epidermal Growth Factor receptor (EGFR) and αVß3 integrin, which are pivotal in tumor growth, angiogenesis, and metastasis. Despite the extensive research into and promising outcomes associated with antibody-based therapies, peptides offer a compelling alternative due to their smaller size, ease of modification, and rapid bioavailability, factors which potentially enhance tumor penetration and reduce systemic toxicity. However, the application of peptides in clinical settings has challenges. Their lower binding affinity and rapid clearance from the bloodstream compared to antibodies often limit their therapeutic efficacy and diagnostic accuracy. This overview sets the stage for a comprehensive review of the current research landscape as it relates to EGFR- and integrin αVß3-targeting peptides. We aim to delve into their synthesis, radiolabeling techniques, and preclinical and clinical evaluations, highlighting their potential and limitations in cancer theranostics. This review not only synthesizes the extant literature to outline the advancements in peptide-based agents targeting EGFR and integrin αVß3 but also identifies critical gaps that could inform future research directions. By addressing these gaps, we contribute to the broader discourse on enhancing the diagnostic precision and therapeutic outcomes of cancer treatments.

Evaluation of relationship between TMPRSS2 p.(Val197Met) variant and COVID-19 susceptibility and severity.

BACKGROUND: The World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a global pandemic on March 11, 2020. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has killed millions of people and had a terrible effect on society. The transmembrane protease serine 2 (TMPRSS2) enzyme is essential in the initial phases of the interplay between the SARSCoV-2 and the host cells by assisting viral entrance. METHODS: This observational case-control study involved 150 participants, 100 adult patients with COVID-19, 50 of whom appeared healthy and had no history of or symptoms of COVID-19 infection when the study was conducted. Between January and April 2022, patients were taken as inpatients in isolation units or through recruitment from the COVID-19 clinic at Kasr Al-Ainy Cairo University Hospitals. According to the National Institutes of Health guidelines (2021), they were categorised into three categories: mild, moderate, and severe. TMPRSS2 p.(Val197Met) variant genotyping was evaluated using TaqMan Real-Time PCR. RESULTS: The study showed a substantial difference between the mild and severe COVID-19 patient groups regarding their TMPRSS2 (p.Val197Met) genotypes (P value = 0.046). The C allele was significantly more prevalent in the mild, moderate and severe COVID-19 patient categories (77.8%, 89.7% and 91.7%, respectively) and the control group (80%). Meanwhile, the T allele was more prevalent in the mild (22.2%) and control (20%) groups. There was a statistically significant difference in allelic distribution between the mild and severe groups (P value = 0.034). CONCLUSION: The study showed a connection between the TMPRSS2 gene variant p.(Val197Met) and the degree of illness. We concluded that the T(mutant) allele was protective against severe COVID-19 because it was linked to lesser disease severity.

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI. METHODS: In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice. RESULTS: Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment. CONCLUSIONS: All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.

The assessment of the protective impact of spidroin extract against UV-A radiation damage by using earthworms (Aporrectodea caliginosa) as a robust human skin model via macroscopic and histological observations.

Numerous studies have confirmed the damage caused by excessive exposure to ultraviolet-A rays. Malignant melanoma and skin cancer are two of the most serious health consequences. Thus, the UV-A protectant is intended to protect the skin, especially the two primary layers of skin (epidermis that represents the interface between the body and its surroundings and dermis). Spider silk is the most powerful natural fibre due to its regeneration, biocompatibility, antimicrobial, wound healing, antiseptic, and blood clotting properties. This work targeted to determine the protective effect of spidroin extract against UV-A radiation damage. Earthworms Aporrectodea caliginosa were collected from Assiut University's farm. Each set of ten earthworms was separated into six groups and placed in a plastic container. Webs of spiders collected from trees and old houses. Spidroin was extracted and utilised in this work to determine the potential effects of topical application on UV-A protection. The experiment is divided into two sections: (1) UV-A exposure and (2) the use of spidroin extract to protect the earthworms from ultraviolet radiation. Two control groups (1،2) of worms were not received UV-A exposure, and four groups (3,4,5,6) were exposed to UVR-A. In contrast, groups (5,6) were received spidroin extract before exposure to UV-A. Each group from the groups (3,4,5,6) was exposed for three consecutive days (» hour/day, ½ hour/day, and 1 h/day), using a UV-Lamp with a wavelength of 366 nm. The histopathological changes revealed that after 1/4 h of UV exposure, the cuticle was swollen with a slightly detached epithelium. The cuticle was down after 1/2 h of exposure, and the epidermis was totally damaged and necrosed. After 1 h, the exposure showed destruction of the epidermis in the circular muscle with a loss of muscle filament integrity, varying size, and altered nucleus form, along with mild disintegration of longitudinal muscle. Spidroin extract is critical for earthworm protection against UV-A radiation damage and able to regeneration. For the first time, morphological and histological analysis was established to detect the Spidroin extract evaluated for topical application on earthworms. Earthworms can be considered as a robust human skin model prior to UV-A exposure. It induces a complete protective effect against UV-A radiation damage in earthworms.

Modulation of cell cycle progression and chromatin dynamic as tolerance mechanisms to salinity and drought stress in maize.

Salinity and drought are the major abiotic stresses that disturb several aspects of maize plants growth at the cellular level, one of these aspects is cell cycle machinery. In our study, we dissected the molecular alterations and downstream effectors of salinity and drought stress on cell cycle regulation and chromatin remodeling. Effects of salinity and drought stress were determined on maize seedlings using 200 mM NaCl (induced salinity stress), and 250 mM mannitol (induced drought stress) treatments, then cell cycle progression and chromatin remodeling dynamics were investigated. Seedlings displayed severe growth defects, including inhibition of root growth. Interestingly, stress treatments induced cell cycle arrest in S-phase with extensive depletion of cyclins B1 and A1. Further investigation of gene expression profiles of cell cycle regulators showed the downregulation of the CDKA, CDKB, CYCA, and CYCB. These results reveal the direct link between salinity and drought stress and cell cycle deregulation leading to a low cell proliferation rate. Moreover, abiotic stress alters chromatin remodeling dynamic in a way that directs the cell cycle arrest. We observed low DNA methylation patterns accompanied by dynamic histone modifications that favor chromatin decondensation. Also, the high expression of DNA topoisomerase 2, 6 family was detected as consequence of DNA damage. In conclusion, in response to salinity and drought stress, maize seedlings exhibit modulation of cell cycle progression, resulting in the cell cycle arrest through chromatin remodeling.

Evaluation of growth and nutritional value of Brassica microgreens grown under red, blue and green LEDs combinations.

Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplements. Growth characterization, nutritional composition profile of 21 varieties representing five species of the Brassica genus as microgreens were assessed under light-emitting diodes (LEDs) conditions. Microgreens were grown under four different LEDs ratios (%); red:blue 80:20 and 20:80 (R80 :B20 and R20 :B80 ), or red:green:blue 70:10:20 and 20:10:70 (R70 :G10 :B20 and R20 :G10 :B70 ). Results indicated that supplemental lighting with green LEDs (R70 :G10 :B20 ) enhanced vegetative growth and morphology, while blue LEDs (R20 :B80 ) increased the mineral and vitamin contents. Interestingly, by linking the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was the green LEDs combination (R70 :G10 :B20 ). Remarkably, under the green LEDs combination (R70 :G10 :B20 ) conditions, the microgreens of Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi and Cabbage green, which can benefit human health in conditions with limited food, had the highest growth and nutritional content.

Chemical and biological assessment for Egyptian surface freshwater environment with reference to human activities.

The Egyptian freshwater was assessed in the River Nile, branches, main canals and certain drainages in eight Governorates, over eight successive seasons starting from spring 2008. Chemical assessment was made through ten parameters and the biological one was made through macro-invertebrates information. Results showed that means of Cd, Pb, Cu, Hg, Mn, Fe, Ni, Na, K & Ca varied in watercourses seasonally within somewhat narrow ranges, which may exceed the level of concern but with some elevations in branches, Rayahs and canals during certain seasons. Sites showed chemical levels over the permissible one or those gain total points < or = 6.3 according to the biological assessment indicate that very poor habitat or those of Hilsenhoff Biotic Index (HBI) equal to 7-10 indicate that organic pollution were observed in all the studied watercourses reflecting hazard non point source pollution. Damietta branch in the region of Damietta city characterized with elevations in the concentration of most chemicals examined. The percentages of sites that showed chemical level over the permissible one were 70.56% for K, 54.08% for Cu, 50.08% for Na, 22.08% for Cd, 11.36% for Fe, 5.6% for Pb, 1.92% for Ni, 1.12% for Mn, 0.16% for Ca and at last 0.0736% for Hg. The biological assessment was more able to define more polluted sites than did the chemical one. Human activity data revealed that each of the drains, Giza and Qalyubia canals showed the highest item conduction (animal or plant waste, macroscopic pollution and presence of bridges or barriers) and this was co parallel with their highest pollution recordation.

Molluscicidal effect of fenitrothion and anilofos on Lymnaea natalensis and Biomphalaria alexandrina snails and on the free larval stages of Schistosoma mansoni.

Psticides; fenitrothion and anilofos (aniloguard) were testd as molluscicides against Lymnaea natalensis and Biomplhalaria alexandrina. The LC10 & LC90 of fenitrothion was 0.12 & 0.21 ppm for L. nalalensis and 0.17 & .26 ppm for B. alexandrina, respectively. The LC50 & LC90 anilofos was 2.61 & 6.47 ppm for Lymnaea and 3.07 & 8.6 ppm for Biomphalaria. The effect of sublethal concentrations (LC0, LC5 & C10) of Feni-rothion on B. alexandrina growth rate, eggs hatchability and on free larval stages of Schistosonma mansoni (miracidia & cerca-riae) were studied. The results obtained showed that sublethal concentrations of fenitrothion caused reduction in growth rate of B. alexandrina and reduction in the hatchibility of snails eggs. The mortality rates of miracidia and cercariae were elevated by increasing both the concentrations of fenitrothion and the time of exposure. The results showed that fenitrothion was more toxic to the free larval stages of S. mansoni than to their snails. The results showed a significant reduction in total protein of treated snails when compared with controls in haemolymph while there was an increase of protein contents of the tissue. The AlkP enzyme activity was slightly increased in the haemolymph of experimental groups than the control and in the tissues the values were significantly higher when compared with control. ALT enzyme activity in haemolymph of experimental groups was higher than controls while its activity in tissue was lower. AST enzyme activity was higher in haemolymph and tissue of experimental groups than in controls.

Semi field trials to control Biomphalaria alexandrina by different modes of exposure to certain plant and chemical molluscicides.

Semi-field trials were carried out in Snail Research Station under simulated natural conditions to evaluate different modes of exposure to Anagallis arvensis and Calendula micrantha as plant molluscicides and bayluscide and copper sulphate as chemical molluscicides. Firstly, B. alexandrina were exposed to the tested molluscicides alone and in addition to two densities of aquatic plants. No apparent effect of aquatic plants on the activity of both plant and chemical molluscicides, this may be due that the two densities of the aquatic plants used were insufficient to interfere with the molluscicides action. Secondly, snails were pre-exposed to three sub-lethal concentrations of the plant molluscicides for 24h then to three concentrations of the chemical molluscicides and vice versa. The results indicate that the pre-exposure increases the snail mortality significantly in all treatments of bayluscide and A. arvensis (except in the highest concentration when the snails firstly exposed to bayluscide then to A. arvensis, where the two compared treatment showed 100%) and in all treatments of bayluscide and C. micrantha. Also, in one treatment of copper sulphate and A. arvensis (in the highest concentration when the snails firstly exposed to A. arvensis then to copper sulphate) and in three treatments of copper sulphate and C. micrantha, (in least and moderate concentrations when snails firstly exposed to C. micrantha then to copper sulphate and in the highest concentration when snails firstly exposed to copper sulphate then to C. micrantha). Thirdly, snails were exposed to mixtures of six different ratios of bayluscide and each of A. arvensis and C. micrantha. The results indicated that the snail mortality increased significantly only in the first treatment of bayluscide and A. arvensis mixtures and in treatment number 6 of bayluscide and C. micrantha.

Partial laser arytenoidectomy in the management of bilateral vocal fold immobility. A modification based on functional anatomical study of the cricoarytenoid joint.

OBJECTIVES: To establish the anatomical relationships of the arytenoid and cricoid cartilages and apply these findings to design an arytenoidectomy based on a sound anatomical basis. METHODS: We prospectively conducted this study between 1996 and 2002 at the Main University Hospital of Alexandria, Egypt. In 50 patients, we endoscopically measured the length of the vocal process and the distance between the vocal process tip and upper border of the cricoid cartilage. We sagittally and axially sectioned 25 total laryngectomy specimens to verify the position of the arytenoids and their relation to the cricoid. The anatomical findings led to the design of a laser partial arytenoidectomy and cordotomy (L-PAC), which we used in 45 patients with bilateral cord paralysis in adduction. RESULTS: The anatomical findings showed that the cricoarytenoid joint did not contribute to the airway in any of the measured specimens. Using L-PAC, we decannulated 100% of the patients and no patient needed postoperative tracheostomy at any time. Only 3 patients experienced minimal postoperative aspiration to liquids (6.7%). We achieved reasonable phonation as assessed by a speech analysis battery. However, 3 patients (6.7%) needed contralateral L-PAC. CONCLUSION: The present extra-articular technique, L-PAC, showed its superiority to previous endoscopic or transcervical complete arytenoidectomy techniques in providing an effective balance between the protective, respiratory, and to a lesser extent the phonatory functions.

Effect of sublethal concentrations of Atriplex halimus (Chenopediaceae) on Biomphalaria alexandrina, the snail-vector of Schistosoma mansoni in Egypt.

Effect of sublethal concentrations of Atriplex halimus on the mortality rate, longevity, egg production of Biomphalaria alexandrina and hatchability of their eggs were studied. The sublethal concentrations of Atriplex caused reduction in survival rates, longevity and egg production of B. alexandrina. Hatchability of snail eggs exposed to tested plant was decreased by increasing its concentrations.

Effect of two herbicides on some biological and biochemical parameters of Biomphalaria alexandrina.

The herbicides, Butachlor and Fluazifop-p-butyl were evaluated against B. alexandrina and their infection with S. mansoni, as well as against the miracidia and cercariae. The tested herbicides reduced the survival and infection rates of B. alexandrina by 28% and 35.71% for Butachlor and 50% and 64% for Fluazifop-p-butyl, respectively. These herbicides significantly reduced the production and duration of cercairal shedding per infected snails. The mortality rates of miracidia and cercariae were elevated gradually by increasing the sub-lethal concentrations of herbicides being 63% and 62%, respectively, after 6 hours of exposure to 6.5 ppm of Butachlor. The protein, glycogen and lipid contents in the snail Soft tissues were significantly reduced. There was a significant elevation in the levels of acid and alkaline phosphatases in haemolymph of snails exposed to Butachlor, 0.05 and 0.48 u/mg protein, respectively.