The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association.

INTRODUCTION: Bladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. MATERIAL AND METHODS: A total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. RESULT: In high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. CONCLUSION: The upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Pharmacological benefits of durva swaras (Cynodon dactylon L. Pers.) administration in APAP-induced liver injury model of mice - Assessment by metabolic and inflammatory markers.

OBJECTIVE: Liver derangement underlies the development of metabolic syndrome in perimenopause. Previously, we have observed that durva swaras (DS) improved metabolic-associated fatty liver disease (MAFLD) and abnormal liver enzymes (aspartate aminotransferase and alanine aminotransferase) along with other complications of menopause in ovariectomized rats. We aimed to decipher the hepatoprotective mechanisms of DS in acetaminophen (APAP)-induced liver injury model, which is analogous to the pathophysiology of MAFLD. MATERIALS AND METHODS: Male Swiss albino mice were distributed into three groups at random. Group I (Control) was administered with vehicle (distilled water) for 7 days. Group II (APAP) received vehicle for the first 6 days and APAP (350 mg/kg - single dose) on the 7th day. Group III (APAP + D) received test compound DS (quality complied) at a dose of 133 mg/kg for 6 days and APAP (350 mg/kg - single dose) on the 7th day. Subsequently, blood and liver tissues were subjected to biochemical, ultrastructural, and gene expression analysis. RESULTS: DS pretreatment protected the liver from APAP-induced disruption of sinusoids and necrosis. DS prevented the elevation of liver enzymes - AST and ALT induced by APAP. Importantly, DS inhibited the APAP-elicited increase in messenger ribonucleic acid levels of hepatic nuclear factor-kappa beta (NF-κB) and pro-inflammatory cytokines, namely interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha. Moreover, DS activated gene expression of nuclear factor erythroid 2-related factor 2 and liver-X-receptor-alpha (LXR-α) to combat the liver damage. CONCLUSION: DS hinders APAP-induced liver damage by activating LXR-α and inhibiting the NF-κB-associated pro-inflammatory cytokine gene expression. These observations confirm the protective role of DS in metabolic dysfunction-associated liver conditions.

A randomized controlled trial on triamcinolone versus saline impregnated merocel post endoscopic sinus surgery: Our experience in a tertiary care centre.

Purpose: To assess the potential benefit of impregnating Merocel (a non-absorbable nasal dressing) with a topical steroid solution, for use as a direct and slow local delivery system of steroids after sinus surgery to improve postoperative wound healing. Methods: In this randomized controlled trial, 40 patients with bilateral chronic rhinosinusitis with nasal polyposis were subjected to functional endoscopic sinus surgery. Following the completion of the surgery, Merocel packs were inserted in the bilateral nasal cavities and infiltrated with 4 mL triamcinolone (40 mg/mL) in one nasal cavity (treatment group) and 4 mL normal saline in the other (control group). Nasal packs were removed on the third postoperative day and postoperative healing assessment was done on postoperative Weeks 1, 2, 4, and 12. The findings were noted as per Lund Kennedy (LKES) and perioperative sinus endoscopy (POSE) scores and compared on both sides. Results: Significant (P < 0.05) improvement was noted in Lund Kennedy score for crusting and polyp at Week 12, for edema at Week 1, and nasal discharge at Weeks 1 and 12, but there was no significant improvement in scarring at any week. Overall, the difference between the treatment and control arms was statistically significant at all postoperative visits except at Week 4. Also, there was a significant improvement in POSE scores at Weeks 1, 2, and 12 but not at Week 4. Conclusion: This study positively concludes that the nasal cavity packed with drug-soaked packs had less scarring and edema in the postoperative period and the overall wound healing was much better as compared to saline-soaked packs.

Estimation of the crop evapotranspiration for Udham Singh Nagar district using modified Priestley-Taylor model and Landsat imagery.

The main challenges for utilizing daily evapotranspiration (ET) estimation in the study area revolve around the need for accurate and reliable data inputs, as well as the interpretation of ET dynamics within the context of local agricultural practices and environmental conditions. Factors such as cloud cover, atmospheric aerosols, and variations in land cover pose challenges to the precise estimation of ET from remote sensing data. This research aimed to utilize Landsat 8 and 9 datasets from the 2022-23 period in the Udham Singh Nagar district to apply the modified Priestley-Taylor (MPT) model for estimating ET. An average ET was estimated 1.33, 1.57, 1.70, 2.99, and 3.20 mm day-1 with 0.29, 0.33, 0.41, 0.69, and 1.03 standard deviation for December, January, February, March, and April month, respectively. In the validation phase, a strong correlation was found between the evaporative fraction derived from MPT and that observed by lysimeter, with R2 = 0.71, mean biased error = 0.04 mm day-1, root mean squared error = 0.62 mm day-1 and agreement index of 0.914. These results collectively support the effectiveness of the MPT model in accurately estimating ET across Udham Singh Nagar district. In essence, this research not only confirms the MPT model's capability in ET estimation but also offers detailed insights into the spatial and temporal fluctuations of energy fluxes and daily ET rates.

Physiological Basis of Plant Growth Promotion in Rice by Rhizosphere and Endosphere Associated Streptomyces Isolates from India.

This study demonstrated the plant growth-promoting capabilities of native actinobacterial strains obtained from different regions of the rice plant, including the rhizosphere (FT1, FTSA2, FB2, and FH7) and endosphere (EB6). We delved into the molecular mechanisms underlying the beneficial effects of these plant-microbe interactions by conducting a transcriptional analysis of a select group of key genes involved in phytohormone pathways. Through in vitro screening for various plant growth-promoting (PGP) traits, all tested isolates exhibited positive traits for indole-3-acetic acid synthesis and siderophore production, with FT1 being the sole producer of hydrogen cyanide (HCN). All isolates were identified as members of the Streptomyces genus through 16S rRNA amplification. In pot culture experiments, rice seeds inoculated with strains FB2 and FTSA2 exhibited significant increases in shoot dry mass by 7% and 34%, respectively, and total biomass by 8% and 30%, respectively. All strains led to increased leaf nitrogen levels, with FTSA2 demonstrating the highest increase (4.3%). On the contrary, strains FB2 and FT1 increased root length, root weight ratio, root volume, and root surface area, leading to higher root nitrogen content. All isolates, except for FB2, enhanced total chlorophyll and carotenoid levels. Additionally, qRT-PCR analysis supported these findings, revealing differential gene expression in auxin (OsAUX1, OsIAA1, OsYUCCA1, OsYUCCA3), gibberellin (OsGID1, OsGA20ox-1), and cytokinin (OsIPT3, OsIPT5) pathways in response to specific actinobacterial treatments. These actinobacterial strains, which enhance both aboveground and belowground crop characteristics, warrant further evaluation in field trials, either as individual strains or in consortia. This could lead to the development of commercial bioinoculants for use in integrated nutrient management practices.

Radiobiological analysis of VMAT treatment plan with flattened and flattening filter free photon beam: an EUD and TCP based comparative study.

Background: This study aimed to evaluate the dosimetric and radiobiological differences between 6MV flattened filter (FF) and flattening filter free (FFF) using volumetric modulated arc (VMAT) technique for head and neck (H&N) cancer patients. Materials and methods: Fifteen patients with H&N carcinoma were selected and treated with VMAT with FF (VMATFF) treatment plan. Retrospectively, additional VMAT treatment plans were developed using FFF beams (VMATFFF). Radiobiological parameters, such as equivalent uniform dose (EUD), tumor cure probability (TCP), and normal tissue complication probability (NTCP), were calculated using Niemierko's model for both VMATFF and VMATFFF. Correlation between dosimetric and radiobiological data were analyzed and compared. Results: The conformity index (CI) was 0.975 ± 0.014 (VMATFF) and 0.964 ± 0. 019 (VMATFFF) with p ≥ 0.05. Statistically, there was an insignificant difference in the planning target volume (PTV) results for TCP (%) values, with values of 81.20 ± 0.88% (VMATFF) and 81.01 ± 0.92 (%) (VMATFF). Similarly, there was an insignificant difference in the EUD (Gy) values, which were 71.53 ± 0.33 Gy (VMATFF) and 71.46 ± 0.34 Gy (VMATFFF). The NTCP values for the spinal cord, left parotid, and right parotid were 6.54 × 10-07%, 8.04%, and 7.69%, respectively, in the case of VMATFF. For VMATFFF, the corresponding NTCP values for the spinal cord, parotids left, and parotid right were 3.09 × 10-07%, 6.57%, and 6.73%, respectively. Conclusion: The EUD and Mean Dose to PTV were strongly correlated for VMATFFF. An increased mean dose to the PTV and greater TCP were reported for the VMATFF, which can enhance the delivery of the therapeutic dose to the target.

The effect of Jordanian essential oil from coriander seeds on antioxidant, anti-inflammatory, and immunostimulatory activities using RAW 246.7 murine macrophages.

Coriander (Coriandrum sativum L.) is a member of the Umbelliferae/Apiaceae family and one of the well-known essential oil-containing plants, in which the seeds are used in traditional medicine, and as flavoring in food preparation. Knowing the diverse chemical components of different parts of the plant, this work aims to investigate the antioxidant, the anti-inflammatory, and the immunostimulatory modulator effects of the Jordanian C. sativum's seed extracted essential oil (JCEO). Coriander oil extract was prepared by hydro-distillation method using the Clevenger apparatus. Different concentrations of coriander oil were examined by using DPPH radical scavenging assay, MTT assay, pro-inflammatory cytokine (Tumor Necrosis Factor-TNF-alpha) production in RAW264.7 murine macrophages in addition, scratch-wound assessment, NO level examination, Th1/Th2 assay, phagocytosis assay, and fluorescence imaging using DAPI stain were conducted. JCEO had a potential metabolic enhancer effect at a concentration of 0.3 mg/mL on cell viability with anti-inflammatory activities via increasing cytokines like IL-10, IL-4, and limiting NO, INF-γ, and TNF-α release into cell supernatant. Antioxidant activity was seen significantly at higher concentrations of JCEO reaching 98.7% when using 100mg/mL and minimally reaching 50% at 12.5mg/mL of the essential oil. Treated macrophages were able to attain full scratch closure after 48-hrs at concentrations below 0.3mg/mL. The seed-extracted JCEO showed significant free radical scavenging activity even at lower dilutions. It also significantly induced an anti-inflammatory effect via an increase in the release of cytokines but reduced the LPS-induced NO and TNF-α production at 0.16-0.3mg/mL. In summary, coriander essential oil demonstrated antioxidant, anti-inflammatory, and immunostimulatory effects, showcasing its therapeutic potential at specific concentrations. The findings underscore its safety and metabolic enhancement properties, emphasizing its promising role in promoting cellular health.

Chronic neuropathic pain components in whiplash-associated disorders correlate with metabolite concentrations in the anterior cingulate and dorsolateral prefrontal cortex: a consensus-driven MRS re-examination.

Introduction: Whiplash injury (WHI) is characterised by a forced neck flexion/extension, which frequently occurs after motor vehicle collisions. Previous studies characterising differences in brain metabolite concentrations and correlations with neuropathic pain (NP) components with chronic whiplash-associated disorders (WAD) have been demonstrated in affective pain-processing areas such as the anterior cingulate cortex (ACC). However, the detection of a difference in metabolite concentrations within these cortical areas with chronic WAD pain has been elusive. In this study, single-voxel magnetic resonance spectroscopy (MRS), following the latest MRSinMRS consensus group guidelines, was performed in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and occipital cortex (OCC) to quantify differences in metabolite concentrations in individuals with chronic WAD with or without neuropathic pain (NP) components. Materials and methods: Healthy individuals (n = 29) and participants with chronic WAD (n = 29) were screened with the Douleur Neuropathique 4 Questionnaire (DN4) and divided into groups without (WAD-noNP, n = 15) or with NP components (WAD-NP, n = 14). Metabolites were quantified with LCModel following a single session in a 3 T MRI scanner within the ACC, DLPFC, and OCC. Results: Participants with WAD-NP presented moderate pain intensity and interference compared with the WAD-noNP group. Single-voxel MRS analysis demonstrated a higher glutamate concentration in the ACC and lower total choline (tCho) in the DLPFC in the WAD-NP versus WAD-noNP group, with no intergroup metabolite difference detected in the OCC. Best fit and stepwise multiple regression revealed that the normalised ACC glutamate/total creatine (tCr) (p = 0.01), DLPFC n-acetyl-aspartate (NAA)/tCr (p = 0.001), and DLPFC tCho/tCr levels (p = 0.02) predicted NP components in the WAD-NP group (ACC r 2 = 0.26, α = 0.81; DLPFC r 2 = 0.62, α = 0.98). The normalised Glu/tCr concentration was higher in the healthy than the WAD-noNP group within the ACC (p < 0.05), but not in the DLPFC or OCC. Neither sex nor age affected key normalised metabolite concentrations related to WAD-NP components when compared to the WAD-noNP group. Discussion: This study demonstrates that elevated glutamate concentrations within the ACC are related to chronic WAD-NP components, while higher NAA and lower tCho metabolite levels suggest a role for increased neuronal-glial signalling and cell membrane dysfunction in individuals with chronic WAD-NP components.

Carbonized Polymer Dot-Tannic Acid Nanoglue: Tissue Reinforcement with Concurrent Fluorescent Tracking, Insulin Delivery, and Reactive Oxygen Species Regulation for Normal and Diabetic Wound Healing.

Nanotizing biosealant components offer a multitude of chemical functionalities for superior adhesion-cohesion, delivering unique properties for comprehensive wound healing that are otherwise impossible to achieve using commercial variants. For the first time, a two-step controlled hydrothermal pyrolysis is reported to nanotize dopamine, phloroglucinol, and glutaraldehyde into carbon dot (CD) to be subsequently converted into carbonized polymer dot (CPD) with gelatin as a co-substrate. Chemical crosslinking of CD with gelatin through Schiff base formation before the second pyrolysis step ensures a complex yet porous polymeric network. The retention of chemical functionalities indigenous to CD substrates and gelatin along with the preservation of CD photoluminescence in CPD for optical tracking is achieved. A unique nanoformulation is created with the CPD through tannic acid (TA) grafting evolving CPD-TA nanoglue demonstrating ≈1.32 MPa strength in lap shear tests conducted on porcine skin, surpassing traditional bioadhesives. CPD-TA nanoglue uploaded insulin as chosen cargo disbursal at the wound site for healing normal and in vitro diabetic wound models using HEKa cells with extraordinary biocompatibility. Most importantly, CPD-TA can generate reactive oxygen species (ROS) and scavenge simultaneously under ambient conditions (23 W white LED or dark) for on-demand sterilization or aiding wound recovery through ROS scavenging.

Bacterial Persister Cells and Development of Antibiotic Resistance in Chronic Infections: An Update.

The global issue of antimicrobial resistance poses significant challenges to public health. The World Health Organization (WHO) has highlighted it as a major global health threat, causing an estimated 700,000 deaths worldwide. Understanding the multifaceted nature of antibiotic resistance is crucial for developing effective strategies. Several physiological and biochemical mechanisms are involved in the development of antibiotic resistance. Bacterial cells may escape the bactericidal actions of the drugs by entering a physiologically dormant state known as bacterial persistence. Recent findings in this field suggest that bacterial persistence can be one of the main sources of chronic infections. The antibiotic tolerance developed by the persister cells could tolerate high levels of antibiotics and may give rise to persister offspring. These persister offspring could be attributed to antibiotic resistance mechanisms, especially in chronic infections. This review attempts to shed light on persister-induced antibiotic resistance and the current therapeutic strategies.

Structural insights into strigolactone catabolism by carboxylesterases reveal a conserved conformational regulation.

Phytohormone levels are regulated through specialized enzymes, participating not only in their biosynthesis but also in post-signaling processes for signal inactivation and cue depletion. Arabidopsis thaliana (At) carboxylesterase 15 (CXE15) and carboxylesterase 20 (CXE20) have been shown to deplete strigolactones (SLs) that coordinate various growth and developmental processes and function as signaling molecules in the rhizosphere. Here, we elucidate the X-ray crystal structures of AtCXE15 (both apo and SL intermediate bound) and AtCXE20, revealing insights into the mechanisms of SL binding and catabolism. The N-terminal regions of CXE15 and CXE20 exhibit distinct secondary structures, with CXE15 characterized by an alpha helix and CXE20 by an alpha/beta fold. These structural differences play pivotal roles in regulating variable SL hydrolysis rates. Our findings, both in vitro and in planta, indicate that a transition of the N-terminal helix domain of CXE15 between open and closed forms facilitates robust SL hydrolysis. The results not only illuminate the distinctive process of phytohormone breakdown but also uncover a molecular architecture and mode of plasticity within a specific class of carboxylesterases.

Novel quinolone substituted 1,3,4-oxadiazole derivatives: design, synthesis, antimicrobial and anti-inflammatory potential.

A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using (Candida albicans, ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. IR, 1H NMR and Mass spectrometry techniques confirmed the structure of synthesized derivatives. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed significant antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds 4(a-l) did not respond well against Candida albicans fungal strain. The compound (4k) represents high % inhibition against COX-II. The compounds (4f, 4h and 4k) exhibited highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of - 8.4, - 8.6 and - 8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.

Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms.

Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.

Mechanical Stretching of Nature Inspired Linear and Branched Polysaccharide Motifs through Steered Molecular Dynamics.

A variety of 10 polysaccharide motifs comprising naturally inspired sequences of monosaccharide building blocks are studied to understand the inter-relation between their structural and mechanical behaviors. Equilibrium and steered molecular dynamics (SMD) simulations are employed to investigate the stress-strain relationships and the associated conformational flips of the pyranose moieties along the polysaccharide chains. The presence of a variety of glycosidic linkages connecting the diverse monosaccharide units along with chain-branching in some cases induce wide diversity in the carbohydrate-Ramachandran plots of the glycosidic dihedrals. Similar variations are observed in the Cremer-Pople ring puckering patterns across the polysaccharide variants. The work further provides a comparison between the experimentally obtained atomic force microscopic data of mechanical stretching for some polysaccharides with the stress-strain curves generated from our SMD simulations. Out of all the systems studied, pectin having an axial-axial orientation of the glycosidic linkage showed maximum stretching potential, while acetan-M, with an equatorial-equatorial disposition of the glycosidic bond, stretched the least. The experimental Young's modulus of the corresponding natural polysaccharides could be reasonably compared to the values obtained from our simulation models. Force distribution analysis is done to understand the propagation of punctual stress in the polysaccharides under SMD conditions. Changes in local electrophilicity or nucleophilicity of atomic centers in puckered pyranose rings are estimated through the condensed Fukui functions. All of this information can help understand the physical behavior and chemical reactivity of complex polysaccharides in a complicated milieu of electronic and steric effects experienced by them.

Real-time infectious disease endurance indicator system for scientific decisions using machine learning and rapid data processing.

The SARS-CoV-2 virus, which induces an acute respiratory illness commonly referred to as COVID-19, had been designated as a pandemic by the World Health Organization due to its highly infectious nature and the associated public health risks it poses globally. Identifying the critical factors for predicting mortality is essential for improving patient therapy. Unlike other data types, such as computed tomography scans, x-radiation, and ultrasounds, basic blood test results are widely accessible and can aid in predicting mortality. The present research advocates the utilization of machine learning (ML) methodologies for predicting the likelihood of infectious disease like COVID-19 mortality by leveraging blood test data. Age, LDH (lactate dehydrogenase), lymphocytes, neutrophils, and hs-CRP (high-sensitivity C-reactive protein) are five extremely potent characteristics that, when combined, can accurately predict mortality in 96% of cases. By combining XGBoost feature importance with neural network classification, the optimal approach can predict mortality with exceptional accuracy from infectious disease, along with achieving a precision rate of 90% up to 16 days before the event. The studies suggested model's excellent predictive performance and practicality were confirmed through testing with three instances that depended on the days to the outcome. By carefully analyzing and identifying patterns in these significant biomarkers insightful information has been obtained for simple application. This study offers potential remedies that could accelerate decision-making for targeted medical treatments within healthcare systems, utilizing a timely, accurate, and reliable method.

Survival of Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes in Ready-to-Eat "Guacamole": Role of Added Antimicrobials.

Ensuring the microbiological safety of food products is majorly important to regulatory agencies, producers, and consumers. This study aimed to examine the effects of three different antimicrobial agents, including chitosan (CH), mastic oil (M), and citric acid (CA), individually or as a combination, against Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes (artificially inoculated) in Guacamole, a ready-to-eat (RTE) avocado-based salad. The Guacamole samples included untreated samples, designated as CNL, and samples treated as follows: CA 0.15% and CA 0.30% with citric acid added at 0.15% and 0.30% v/w; CH 0.5% and CH 1% with chitosan at 0.5 and 1% v/w; M 0.2% and M 0.4% with mastic essential oil (EO) at 0.2% and 0.4% v/w; CACH with CA 0.30% and CH 1% v/w; CAM with CA 0.30% and M 0.4% v/w; CHM with CH 1% and M 0.4% v/w; and CACHM with CA 0.30%, CH 1%, and M 0.4% v/w. Microbiological evaluation, monitoring of the pH values, and proximate analyses (moisture, fat, protein, ash, and water activity) were performed at different time intervals (days 0, 1, 3, 5, and 7) at two storage temperatures (4 and 10 °C). Antimicrobial treatments, particularly CH 1% and CACHM, effectively (p < 0.05) reduced Salmonella spp. and E. coli O157:H7 populations at 4 °C, while CACHM showed the most efficacy against L. monocytogenes. However, at 10 °C, antimicrobials had limited impact, and the bacterial counts exhibited an increasing trend during storage. The pH values in the avocado-based salad samples showed, in general, higher decreases at 10 compared to 4 °C, with the CHM combination showing the highest antimicrobial effect.

Transcriptomic response of prostate cancer cells to carbon ion and photon irradiation with focus on androgen receptor and TP53 signaling.

BACKGROUND: Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling. METHODS: Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis. RESULTS: Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified. CONCLUSION: Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle.

Phytoconstituents as modulators of NF-κB signalling: Investigating therapeutic potential for diabetic wound healing.

The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds.

Shielding against breast tumor relapse with an autologous chemo-photo-immune active Nano-Micro-Sera based fibrin implant.

Local recurrence post-surgery in early-stage triple-negative breast cancer is a major challenge. To control the regrowth of a residual tumor, we have developed an autologous therapeutic hybrid fibrin glue for intra-operative implantation. Using autologous serum proteins as stabilizers, we have optimized high drug-loaded lapatinib-NanoSera (Lap-NS; ∼66% L.C.) and imiquimod-MicroSera (IMQ-MS; ∼92% L.C). Additionally, plasmonic nanosera (PNS) with an ∼67% photothermal conversion efficiency under 980 nm laser irradiation was also developed. While localized monotherapy with either Lap-NS or PNS reduced the tumor regrowth rate, their combination with IMQ-MS amplified the effect of immunogenic cell death with a high level of tumor infiltration by immune cells at the surgical site. The localized combination immunotherapy with a Nano-MicroSera based hybrid fibrin implant showed superior tumor inhibition and survival with significant promise for clinical translation.

Diastereoselective cyclopropanation of α,ß-unsaturated carbonyl compounds with vinyl sulfoxonium ylides.

Herein, we report a three-component stereoselective cyclopropanation of vinyl sulfoxonium ylides with indane 1,3-dione and aldehydes under mild reaction conditions. In contrast to previous reports, the present work shows that electrophilic addition selectively takes place at the α-position of the vinyl sulfoxonium ylide. The interesting feature of this approach is that the multicomponent reaction selectively proceeds because of the difference in nucleophilic reactivity of vinyl sulfoxonium ylides and indane 1,3-dione with electrophilic partners, such as aldehydes and in situ generated arylidenes. Additionally, density functional theory (DFT) studies were conducted to investigate the difference in the reactivity of these reactants, as well as to unveil the mechanism of this three-component reaction. Furthermore, non-covalent interactions of selectivity-determining transition states explain the origin of the diastereoselectivity of cyclopropanation.