Comprehensive insight into exploring the potential of microbial enzymes in cancer therapy: Progress, challenges, and opportunities: A review.

Microbial enzymes are crucial catalysts in various industries due to their versatility and efficiency. The microbial enzymes market has recently expanded due to increased demand for many reasons. Among them are eco-friendly solutions, developing novel microbial strains with enhanced enzymes that perform under harsh conditions, providing sustainability, and raising awareness about the benefits of enzyme-based products. By 2030, the global enzyme market is expected to account for $525 billion, with a growth rate of 6.7 %. L-asparaginase and L-glutaminase are among the leading applied microbial enzymes in antitumor therapy, with a growing market share of 16.5 % and 9.5 %, respectively. The use of microbial enzymes has opened new opportunities to fight various tumors, including leukemia, lymphosarcoma, and breast cancer, which has increased their demand in the pharmaceutical and medicine sectors. Despite their promising applications, commercial use of microbial enzymes faces challenges such as short half-life, immunogenicity, toxicity, and other side effects. Therefore, this review explores the industrial production, purification, formulation, and commercial utilization of microbial enzymes, along with an overview of the global enzyme market. With ongoing discoveries of novel enzymes and their applications, enzyme technology offers promising avenues for cancer treatment and other therapeutic interventions.

The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients.

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

Tumor-Agnostic Therapy-The Final Step Forward in the Cure for Human Neoplasms?

Cancer accounted for 10 million deaths in 2020, nearly one in every six deaths annually. Despite advancements, the contemporary clinical management of human neoplasms faces a number of challenges. Surgical removal of tumor tissues is often not possible technically, while radiation and chemotherapy pose the risk of damaging healthy cells, tissues, and organs, presenting complex clinical challenges. These require a paradigm shift in developing new therapeutic modalities moving towards a more personalized and targeted approach. The tumor-agnostic philosophy, one of these new modalities, focuses on characteristic molecular signatures of transformed cells independently of their traditional histopathological classification. These include commonly occurring DNA aberrations in cancer cells, shared metabolic features of their homeostasis or immune evasion measures of the tumor tissues. The first dedicated, FDA-approved tumor-agnostic agent's profound progression-free survival of 78% in mismatch repair-deficient colorectal cancer paved the way for the accelerated FDA approvals of novel tumor-agnostic therapeutic compounds. Here, we review the historical background, current status, and future perspectives of this new era of clinical oncology.

The use of proteins and peptides-based therapy in managing and preventing pathogenic viruses.

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and ß) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review.

Synthesis and characterization of chitosan hybridized zinc phosphate/hydroxyapatite core shell nanostructure and its potentiality as delivery system of oxaliplatin drug.

An advanced form of zinc phosphate/hydroxyapatite nanorods with a core-shell structure (ZPh/HPANRs) was made and then hybridized with chitosan polymeric chains to make a safe biocomposite (CH@ZPh/HPANRs) that improves the delivery structure of traditional oxaliplatin (OXPN) chemotherapy during the treatment of colorectal cancer cells. The qualifications of CH@ZPh/HPANRs in comparison with ZPh/HPANRs as a carrier for OXPN were followed based on loading, release, and cytotoxicity. CH@ZPh/HPANRs composite exhibits a notably higher OXPN loading capacity (321.75 mg/g) than ZPh/HPANRs (127.2 mg/g). The OXPN encapsulation processes into CH@ZPh/HPANRs display the isotherm behavior of the Langmuir model (R2 = 0.99) and the kinetic assumptions of pseudo-first-order kinetics (R2 > 0.89). The steric studies reflect a strong increment in the quantities of the free sites after the chitosan hybridization steps (Nm = 34.6 mg/g) as compared to pure ZPh/HPANRs (Nm = 18.7 mg/g). Also, the capacity of each site was enhanced to be loaded by 10 OXPN molecules (n = 9.3) in a vertical orientation. The OXPN loading energy into CH@ZPh/HPANRs (<40 KJ/mol) reflects physical loading reactions involving van der Waals forces and hydrogen bonding. The OXPN release profiles of CH@ZPh/HPANRs exhibit slow and controlled properties for about 140 h at pH 7.4 and 80 h at pH 5.5. The release kinetics and diffusion exponent (>0.45) signify non-Fickian transport and a complex erosion/diffusion release mechanism. The free CH@ZPh/HPANRs particles display a considerable cytotoxic effect on the HCT-116 cancer cells (9.53 % cell viability), and their OXPN-loaded product shows a strong cytotoxic effect (1.83 % cell viability).

Mesenchymal stem cell transplantation in burn wound healing: uncovering the mechanisms of local regeneration and tissue repair.

Burn injuries pose a significant healthcare burden worldwide, often leading to long-term disabilities and reduced quality of life. To explore the impacts of the transplantation of mesenchymal stem cells (MSCs) on the healing of burns and the levels of serum cytokines, 60 fully grown Sprague-Dawley rats were randomly divided into three groups (n = 20 each): group I (control), group II (burn induction), and group III (burn induction + bone marrow (BM)-MSC transplantation). Groups II and III were further divided into four subgroups (n = 5 each) based on euthanasia duration (7, 14, 21, and 28 days post transplant). The experiment concluded with an anesthesia overdose for rat death. After 7, 14, 21, and 28 days, the rats were assessed by clinical, laboratory, and histopathology investigations. The results revealed significant improvements in burn healing potentiality in the group treated with MSC. Furthermore, cytokine levels were measured, with significant increases in interleukin (IL)-6 and interferon alpha (IFN) observed, while IL-10 and transforming growth factor beta (TGF-ß) decreased at 7 days and increased until 28 days post burn. Also, the group that underwent the experiment exhibited increased levels of pro-inflammatory cytokines and the anti-inflammatory cytokine IL-10 when compared to the control group. Histological assessments showed better re-epithelialization, neovascularization, and collagen deposition in the experimental group, suggesting that MSC transplantation in burn wounds may promote burn healing by modulating the immune response and promoting tissue regeneration.

The effect of hepatic steatosis on 18F-FDG uptake in PET-CT examinations of cancer Egyptian patients.

BACKGROUND: Hepatic steatosis is the most common chronic hepatic disease. Imaging diagnosis of hepatic steatosis has been evaluated as an alternative to invasive histological diagnosis. STUDY AIMS: The study aimed to assess the effect of hepatic steatosis on Flourine-18 fluorodeoxyglucose (18F-FDG) uptakes in cancer patients. PATIENTS AND METHODS: Blood samples were collected from 50 cancer patients and analyzed to calculate fatty liver index and Hepatic steatosis index (HIS). Hepatic steatosis examined using high-resolution ultrasound and positron emission tomography-computed tomography (PET-CT). Linear attenuation coefficient, standardized-uptake value (SUV) mean (SUV mean), and SUV maximum (SUVmax) were measured. Accordingly, patients were divided equally into non-fatty liver, and fatty liver groups. RESULTS: A significant increase in SUVmax and SUV mean was observed in the fatty liver group more than in the non-fatty liver group. HSI significantly increased in the fatty liver group compared to the non-fatty liver group. Liver tissue uptake FDG was significantly correlated with HSI values. SUV max significantly correlated with body mass index (BMI) in the non-fatty group only. CONCLUSION: Hepatic changes in cancer patients affect the liver metabolic activity and thus the 18 F-FDG uptake. Therefore, further corrections should be considered when the liver is used as a comparator for PET-CT scans of cancer patients.

Nanosheet arrays of iron oxide for enhanced ammonia synthesis via electrochemical nitrogen reduction for prospective algal membrane bioreactors.

The earth's nitrogen cycle relies on the effective conversion of nitrogen (N2) to ammonia (NH3). As a result, the research and development of catalysts that are earth-abundant, inexpensive, and highly efficient but do not need precious metals is of the utmost significance. In this investigation, we present a controlled synthesis technique to the fabrication of an iron oxide (Fe2O3) nanosheet array by annealing at temperatures ranging from 350 to 550 °C. This array will be used for the electrochemical reduction of atmospheric N2 to NH3 in electrolytes. The Fe2O3 nanosheet array that was produced as a result displays outstanding electrochemical performance as well as remarkable stability. When compared to a hydrogen electrode working under normal temperature and pressure conditions, the Fe2O3 nanosheet array produces an impressive NH3 production rate of 18.04 g per hour per mg of catalytically active material in 0.1 M KOH electrolyte, exhibiting an enhanced Faradaic efficiency (FE) of 13.5% at -0.35 V. This is accomplished by exhibiting an enhanced Faradaic efficiency (FE) of 0.1 M KOH electrolyte. The results of experiments and electrochemical studies reveal that the existence of cation defects in the Fe2O3 nanosheets plays an essential part in the enhancement of the electrocatalytic activity that takes place during nitrogen reduction reactions (NRR). This study not only contributes to the expanding family of transition-metal-based catalysts with increased electrocatalytic activity for NRR, but it also represents a substantial breakthrough in the design of catalysts that are based on transition metals, so it's a win-win. In addition, the use of Fe2O3 nanosheets as electrocatalysts has a lot of potential in algal membrane bioreactors because it makes nitrogen fixation easier, it encourages algae growth, and it makes nitrogen cycling more resource-efficient.

Modified Capsulorrhaphy Technique in Open Reduction of Developmental Dysplasia of the Hip.

BACKGROUND: Neglected patients with developmental dysplasia of the hip (DDH) are not uncommon. Various treatment modalities have been used. Capsulorrhaphy is one of the most critical steps during the process of open reduction of DDH. Inadequate capsulorrhaphy technique can increase the failure rate of open reduction procedures. This study presented the clinical and radiographic results of using a new capsulorrhaphy technique. METHODS: Between November 2005 and March 2018, 540 DDH in 462 patients were retrospectively reviewed. The mean age at surgery was 31 months. All patients underwent a modified capsulorrhaphy technique developed by the main author (with or without additional pelvic or femoral procedures). Postoperative patient assessment during the follow-up period was performed both clinically and radiologically. RESULTS: Follow-up period ranged between 36 months and 12 years. Based on the modified McKay score, good and excellent outcomes were obtained in 90.3%. Functional results were better in younger age (less than 39 mo). Both acetabular index and lateral center edge angle showed significant improvement at 3 years follow-ups. Proximal femoral growth disturbance (PFGD) was encountered in 92 hips. Classes 2 and 3 did not affect the functional results, whereas patients with PFGD classes 4 and 5 had fair to poor functional outcomes. There were 12 hips with redislocation. Revision was done using the same capsulorrhaphy technique. CONCLUSION: Using the index technique of capsulorrhaphy in DDH surgery is safe, reliable, and yields good functional and radiologic outcomes with a relatively low complication rate. LEVEL OF EVIDENCE: Level IV-therapeutic retrospective case series.

Antagonistic Potentiality of Actinomycete-Derived Extract with Anti-Biofilm, Antioxidant, and Cytotoxic Capabilities as a Natural Combating Strategy for Multidrug-Resistant ESKAPE Pathogens.

The global increase in multidrug-resistant (MDR) bacteria has inspired researchers to develop new strategies to overcome this problem. In this study, 23 morphologically different, soil-isolated actinomycete cultures were screened for their antibacterial ability against MDR isolates of ESKAPE pathogens. Among them, isolate BOGE18 exhibited a broad antibacterial spectrum, so it was selected and identified based on cultural, morphological, physiological, and biochemical characteristics. Chemotaxonomic analysis was also performed together with nucleotide sequencing of the 16S rRNA gene, which showed this strain to have identity with Streptomyces lienomycini. The ethyl acetate extract of the cell-free filtrate (CFF) of strain BOGE18 was evaluated for its antibacterial spectrum, and the minimum inhibitory concentration (MIC) ranged from 62.5 to 250 µg/ml. The recorded results from the in vitro anti-biofilm microtiter assay and confocal laser scanning microscopy (CLSM) of sub-MIC concentrations revealed a significant reduction in biofilm formation in a concentration-dependent manner. The extract also displayed significant scavenging activity, reaching 91.61 ± 4.1% and 85.06 ± 3.14% of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis( 3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), respectively. A promising cytotoxic ability against breast (MCF-7) and hepatocellular (HePG2) cancer cell lines was obtained from the extract with IC50 values of 47.15 ± 13.10 and 122.69 ± 9.12 µg/ml, respectively. Moreover, based on gas chromatography-mass spectrometry (GC-MS) analysis, nine known compounds were detected in the BOGE18 extract, suggesting their contribution to the multitude of biological activities recorded in this study. Overall, Streptomyces lienomycini BOGE18-derived extract is a good candidate for use in a natural combating strategy to prevent bacterial infection, especially by MDR pathogens.

Taurine attenuated methotrexate-induced intestinal injury by regulating NF-κB/iNOS and Keap1/Nrf2/HO-1 signals.

Methotrexate (MTX) is a well-known and widely used cytotoxic chemotherapeutic agent. However, intestinal mucosa damage is a serious adverse effect of MTX. Taurine (TUR) is a sulfur-containing free ß-amino acid with antioxidant and therapeutic value against several diseases. The current study aimed to determine the protective effect of TUR against MTX-induced intestinal injury. Rats were allocated into four groups. The first group received vehicles only. The second group received TUR at a dose of 250 mg/kg i.p. For induction of intestinal injury, the rats in the third group were given MTX once at a dose of 20 mg/kg, i.p. The fourth group received TUR 7 days before and 7 days after MTX, as previously described. TUR significantly attenuated the cytokine release by suppressing NF-κB and iNOS expressions. Moreover, cotreatment with TUR attenuated the increased MDA level while it enhanced the antioxidant GSH and SOD levels mediated by effective downregulation of Keap1 expression, while the expression of Nrf2, HO-1, and cytoglobin were up-regulated. Additionally, TUR mitigated the apoptosis and proliferation indices by decreasing the elevated levels of intestinal PCNA and caspase-3. Finally, TUR potently increased the cytotoxic activity of MTX toward Caco-2, MCF-7, and A549 cancer cells. In conclusion, TUR was a promising agent for relieving MTX-mediated intestinal injury via various antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

The microbiome-derived metabolite TMAO drives immune activation and boosts responses to immune checkpoint blockade in pancreatic cancer.

The composition of the gut microbiome can control innate and adaptive immunity and has emerged as a key regulator of tumor growth, especially in the context of immune checkpoint blockade (ICB) therapy. However, the underlying mechanisms for how the microbiome affects tumor growth remain unclear. Pancreatic ductal adenocarcinoma (PDAC) tends to be refractory to therapy, including ICB. Using a nontargeted, liquid chromatography-tandem mass spectrometry-based metabolomic screen, we identified the gut microbe-derived metabolite trimethylamine N-oxide (TMAO), which enhanced antitumor immunity to PDAC. Delivery of TMAO intraperitoneally or via a dietary choline supplement to orthotopic PDAC-bearing mice reduced tumor growth, associated with an immunostimulatory tumor-associated macrophage (TAM) phenotype, and activated effector T cell response in the tumor microenvironment. Mechanistically, TMAO potentiated the type I interferon (IFN) pathway and conferred antitumor effects in a type I IFN-dependent manner. Delivering TMAO-primed macrophages intravenously produced similar antitumor effects. Combining TMAO with ICB (anti-PD1 and/or anti-Tim3) in a mouse model of PDAC significantly reduced tumor burden and improved survival beyond TMAO or ICB alone. Last, the levels of bacteria containing CutC (an enzyme that generates trimethylamine, the TMAO precursor) correlated with long-term survival in patients with PDAC and improved response to anti-PD1 in patients with melanoma. Together, our study identifies the gut microbial metabolite TMAO as a driver of antitumor immunity and lays the groundwork for potential therapeutic strategies targeting TMAO.

Olmesartan ameliorates cyclophosphamide-induced hemorrhagic cystitis in rats via Nrf2/HO-1 signaling pathway.

Hemorrhagic cystitis (HC) is considered a fatal complication of cyclophosphamide (CP). Down-regulation of Nrf2 and induction of pro-inflammatory mediators are the main pathological factors. Recently, ameliorative potential of the angiotensin II (AII) type-1 (AT1) receptor blocker olmesartan (OLM) on oxidative stress and inflammatory cytokines was reported. The current study aims to investigate the possible protective effect of OLM on CP-induced HC in Wistar rats. The animals were divided into the control group (0.5% W/V carboxymethylcellulose, p.o.); OLM group (20 mg/kg, p.o., for 21 days); CP group (a single dose of 100 mg/kg, i.p.); and the remaining groups that received CP i.p. with oral OLM 5, 10 and 20 mg/kg for 21 days, respectively. The bladder tissue was collected for histopathology, immunohistochemistry, ELISA, Western blot, and oxidative stress assay. The OLM at doses of 10 and 20 mg/kg attenuated increase in TNF-α, IL-6, NF-kB, iNOS, and COX-2 induced by CP. Additionally, it up-regulated the Nrf2/HO-1 pathway, bladder GSH content, and CAT and SOD activities. The data indicated that OLM inhibited ROS-induced NF-kB, which caused inhibition of pro-inflammatory cytokines and activation of the Nrf2/HO-1 pathway. Hence, OLM holds great promise for preventing CP-induced HC.

Effects of insulin and sitagliptin on early cardiac dysfunction in diabetic rats.

AIMS: Cardiac affection is common in diabetic patients. Although insulin exerts a cardioprotective role, it may not be enough to totally prevent this affection. The current study aimed to compare the cardioprotective effect of insulin alone or combined with sitagliptin in a rat model of type 1 diabetes mellitus. MATERIALS AND METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Diabetic rats were treated with insulin (3 IU), insulin (6 IU), or insulin (3 IU) + sitagliptin (10 mg/kg) for 42 days. KEY FINDINGS: Diabetic rats exhibited significant systolic and diastolic cardiac affection with significant elevation of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and brain natriuretic peptide (BNP) levels. Treatment with insulin prevented the deterioration of diabetes-induced cardiac condition, an effect that was significantly potentiated by the combined use of sitagliptin. SIGNIFICANCE: The combined use of sitagliptin and insulin significantly improved the cardioprotective effect of insulin and prevented the early cardiac dysfunction in STZ diabetic rats.

Vanillin attenuates thioacetamide-induced renal assault by direct and indirect mediation of the TGFß, ERK and Smad signalling pathways in rats.

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-ß1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule-1 (KIM-1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α-smooth muscle actin (α-SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α-SMA renal expression and TNFα, IL-6, TGF-ß1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM-1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF-ß type I receptors (ALK5) biding site.

Maximal levator resection versus Gore-Tex® sling for congenital blepharoptosis with poor levator function.

BACKGROUND: Treating congenital blepharoptosis is often mandatory to clear the visual access and avoid amblyopia; however, when the levator function is poor, achieving a satisfactory long-term outcome is challenging. This study aimed to compare the outcomes of maximal levator resection (MLR) with those of frontalis suspension (FS) using Gore-Tex ®, in the treatment of congenital blepharoptosis with poor levator function. PATIENTS AND METHODS: The study included 102 eyelids of 66 patients of mean age 4.3 ± 1.6 standard deviation (SD) years, randomly divided into two groups (51 eyes each). Group A: FS using Gore-Tex ®, Group B: MLR. Postoperative outcomes were evaluated at 1, 6 and 12 months. Patients' ophthalmic examination including margin-reflex distance (MRD1) before and after surgery and postoperative complications were recorded. RESULTS: At the end of the follow-up, the mean MRD1 increased from 0.3 ± 0.7 SD mm in Group A, 0.4 ± 0.8 SD mm in Group B preoperatively, to 2.7 ± 0.5 SD mm and 2.9 ± 0.7 SD mm, respectively (P < 0.001 in both groups). Results of Group B were significantly higher than Group A (P = 0.047). Success was achieved in 77 eyelids (75.4%), distributed as follows: 36 eyelids (70.6%) in Group A, and 41 eyelids (80.1%) in Group B. The total recurrence rate was 6.9% (seven eyes), while other complications were recorded in 23 eyes (22.5%). CONCLUSION: MLR, compared to FS with Gore-Tex® sling, can be a more efficient surgical option to correct congenital blepharoptosis with poor levator excursion. Prominent postoperative lagophthalmos warrants close ocular surface observation in early follow-up weeks.

The incidence and duration of COVID-19 vaccine-related reactive lymphadenopathy on 18F-FDG PET-CT.

OBJECTIVES: Reactive axillary lymph nodes (ALN) may occur post-COVID-19 vaccination. This may be confused with malignant nodal metastases on oncological imaging. We aimed to determine the reactive ALN incidence and duration on 18F-fluorodeoxyglucose positron emission tomography - computed tomography (18F-FDG PET-CT), and its relationship with gender, age and vaccine type. METHODS: A retrospective study was performed. Two-hundred and four eligible patients had 18F-FDG PET-CT between 01 January 2021 and 31 March 2021, post-vaccination with Pfizer-BioNTech or Oxford-AstraZeneca vaccine. Image analysis was performed on dedicated workstations. SPSS was used for statistical analysis. RESULTS: Thirty-six per cent of patients had reactive ALN until 10 weeks post-vaccination; reducing in frequency and intensity with time. Women were more likely to have reactive ALN compared with men. The frequency and intensity were higher in patients aged <65 years compared with those aged ≥65 years. However, no difference was found between both vaccine types in our study cohort. CONCLUSIONS: Physicians' awareness of COVID-19 vaccine-related reactive ALN on 18F-FDG PET-CT is important to avoid inappropriate upstaging of cancers.

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking.

In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds 6b,d-g, and 7b showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound 6e displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, 6e was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound 6e endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.

Antibacterial and cytotoxic potency of thermophilic Streptomyces werraensis MI-S.24-3 isolated from an Egyptian extreme environment.

The need for novel and active antibiotics specially from actinomycetes is essential due to new and drug-resistant pathogens. In this study, 87 actinomycetes were isolated, and 18 strains among them characterized as thermophilic actinomycetes. Further fractionation and preliminary antibacterial activities indicated that one strain, coded as MI-S.24-3, showed good antibacterial activity. Based on the phenotypic, genomic, phylogenetic, and biochemical analyses, MI-S.24-3 was identified as Streptomyces werraensis. Results demonstrated that the ethyl acetate active fraction showed maximum antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC (12.7 ± 0.1 and 18.3 ± 0.2 mg/mL), and MBC (96.5 ± 1.4 and 91.5 ± 0.7 mg/mL), respectively, with determination of time kill kinetics assay. The active fraction showed moderate-to-weak cytotoxic effects against human lung carcinoma (A549 cells), breast cancer cell line (MCF-7), and human cervical carcinoma (HELA cells) with a IC50 of (23.8 ± 1.2, 54 ± 1.8, 96.4 ± 3.2 µg/mL, respectively). Active components were characterised by different chemically volatile, ester, and lactone compounds, determined by GC-MS coupled with daughter ions of (GC-MS/MS). Notably, erucic acid and reynosin identified compounds are rare metabolites produced by Streptomyces werraensis. Our findings demonstrated that the MI-S.24-3 strain could be a potential source for active compounds of biomedical and pharmaceutical interest.