Good Therapeutic Agent Research Articles

Enhanced bacterial disinfection of multi-drug resistance bacteria by PCN@AgI heterojunction under visible light irradiation

Pathogenic bacterial infections have become a continuing threat to human health over the past decade, the development of novel antibacterial agents or strategies against drug-resistance bacteria is highly desirable. Although porphyrin-based metal organic frameworks (PCN) are important photosensitizers (PSs) for photodynamic antibacterial treatments, they are inefficient for killing gram-negative bacteria such as Escherichia coli. Herein, PCN@AgI heterojunction was prepared as a novel and potent multifunctional antibacterial agent to combat bacteria including drug-resistance bacteria such as extended-spectrum β-lactamaseEscherichia coli (ESBL) under visible light irradiation in vitro, attributing to the cooperation of the generated ROS and released Ag+ as well as GSH-depleting ability. Compared to pristine PCN, the formation of heterojunction between AgI and PCN facilitated the sufficient separation of the produced electron- hole pairs, leading to enhanced photocatalytic antibacterial capability by producing sufficient ROS. Furthermore, its GSH-depleting ability due to its oxidase-like behavior further boosted its antibacterial capability. Significantly, in vivo studies demonstrated that PCN@AgI heterojunction could promote the healing of E. coli-infected wound on rice back with high biosafety. These findings manifested that PCN@AgI heterojunction was a good potential antibacterial therapeutic agent and may hold promise in bacteria-infected wound healing.

Hepatoprotective activity of Vitis vinifera L. fruit (V. vinifera) against acetaminophen induced oxidative damage

Liver-related diseases have become a global concern worldwide. Hepatic cells damage is mostly caused by a variety of toxic chemicals like carbon tetrachloride (CCl4), acetaminophen (APAP), antibiotics and thioacetamide. For the treatment of liver diseases, herbal based therapeutics have been used since long time in India and has become popular all over world. But in some places herbal medicines are still not acceptable for the treatment of liver diseases due to limiting factors. V. vinifera has numerous medicinal properties such as it acts as vasoprotective, astringent, diuretic and hepatoprotective activity. Various protocols were followed for the assessment of Vitis vinifera hepatoprotectivity properties including preparation of plants. Protocols include AST, ALT, LPO, GSH, urea, cholesterol, SOD, ATPase etc. The maximum recoupment was found with V. vinifera which was confirmed by % protection. V. vinifera ameliorated APAP induced cell death. It might be due to its antioxidant, radical scavenging and anti-inflammatory actions of V. vinifera. In this present study, we used V. vinifera as hepatoprotective agent which can be used as a good therapeutic agent against liver toxicity and also for the successful development of drug delivery in near future.

Mesalamine may be a Plausible Therapeutic Agent for the Management of Diabetic Wounds: A Computational Approach

Aim: Validation of mesalamine (MS) as a potential therapeutic agent in treating diabetic wound (DW) healing using in silico approach. Background: Diabetic wound (DW) is a serious consequence of diabetes that frequently results in the amputation of the affected organ. Maggot therapy, pressure off-loading, surgical intervention, glucose control, hyperbaric oxygen therapy, wound debridement, and other treatments are currently available for DW. However, the majority of people do not meet all DW requirements due to significant pathology and the high expense of the solutions. Objective: To address the issues with current conventional therapy, we reasoned that repurposing existing medication (MS) to a target receptor that plays a significant role in the progression of DW might be advantageous. Mesalamine (MS), also known as Mesalazine or 5- Aminosalicylic acid, is an aminosalicylate anti-inflammatory used to treat inflammatory bowel disease (IBD), ulcerative colitis (UC), inflamed anus or rectum. The complicated pathophysiology of DW, which includes prolonged inflammation, increased infection, decreased cell proliferation, and migration, is a serious issue. As a result, we chose the MMP-9, TNF-α, MurC, ParE, and GSK-3β receptors as a universal target for treating the complex pathogenesis of DW. The use of MS as a therapeutic modulator on MMP-9, TNF-α, MurC, ParE, and GSK-3β receptors was studied in the current hypothetical investigation. Methods: Computational studies such as molecular docking and MMGBSA were performed by using the Schrödinger suite. Results: Computational investigations, such as molecular docking and MMGBSA were used to test our theory. It is clear from the in silico methods that MS has a higher binding affinity for the designated receptors. Hence, it is predicted that MS may be a good therapeutic agent to use in the treatment of DW. Conclusion: As a result of our findings, MS appears to be a unique therapeutic drug for the treatment of DW. However, further studies are highly required to take MS into clinical use.

Rynchopeterine inhibits the formation of hypertrophic scars by regulating the miR-21/HIF1AN axis

Hypertrophic scar (HS) is a fibroproliferative skin disease characterized by abnormal wound healing and pathological excessive fibrosis of the skin. Currently, the molecular mechanism of the disease is still largely unknown, and there is no effective drug treatment. In this study, we explored the effect of Rynchopeterine on the formation of HS. HS fibroblasts (HSFs) were isolated from the HS tissues of patients recovering from severe burns. After treating HSFs with different concentrations of Rynchopeterine, CCK-8, EdU, and Annexin V-FITC/PI assays were used to detect the proliferation, apoptosis, and contractile ability of HSFs. RT-qPCR and Western blotting were performed to evaluate the effect of Rynchopeterine on the expression of miR-21 and hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). The dual-luciferase reporter gene was used to verify the targeting relationship between miR-21 and HIF1AN. Rynchopeterine reduced the expression of Col1a2, Col3a1, and α-SMA, inhibited proliferation and contraction of HSFs, and increased apoptosis in a dose-dependent manner. miR-21 was highly expressed in HS tissues and HSFs, and Rynchopeterine could inhibit miR-21 expression. Overexpression of miR-21 and knockdown of HIF1AN increased proliferation, activation, contraction, and collagen synthesis of HSFs, and inhibited their apoptosis. In vivo, Rynchopeterine could reduce the collagen content of the dermis and the positive ratio of PCNA and α-SMA. Rynchopeterine is a good therapeutic agent for HS, which up-regulates the expression of HIF1AN by inhibiting miR-21, thereby inhibiting the formation of HS.

Exploring the antibiofilm efficacy of cinnamaldehyde against Malassezia globosa associated pityriasis versicolor

BackgroundMalassezia globosa is a commensal basidiomycetous yeast occurring on the skin that causes pityriasis versicolor (PV) and seborrheic dermatitis, but that has also been implicated in other dermatoses. Cinnamaldehyde (CM) has antibacterial, antioxidant, and anti-inflammatory activities, but the effect of CM on M. globosa-infected PV has not been clarified. PurposeThe study aimed to investigate the possible antifungal and antibiofilm activities of CM against M. globosa-infected PV in vivo and in vitro. MethodsThe broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of CM against M. globosa. The crystal violet staining assay and XTT assay were used to investigate the inhibition of CM on biofilm formation and the eradication of mature biofilms. The visualizations of the biofilm and cell distribution in the biofilm matrix were performed with a scanning electron microscope and confocal laser scanning microscope. The kits of antioxidant kinase were used to determine the activities of oxidative stress markers in M. globosa-stimulated HaCaT cells. Western blot assays were used to evaluate the role of TLR2/NF-κB in vitro. Furthermore, the protective effect of CM was assessed in M. globosa-associated PV mice. The expressions of inflammatory cytokines and apoptosis were screened using ELISA assays. The expressions of interleukin-6 and tumor necrosis factor-α were measured by an immunohistochemistry method in vivo. ResultsOur results showed that the MIC of CM against planktonic cells of M. globosa was 4 µg/ml and treatment with 20 × MIC CM eradicated mature biofilms of M. globosa. In vitro, after CM treatment the levels of oxidative stress indicators (i.e., superoxide dismutase, catalase, glutathione) significantly increased, while the levels of malondialdehyde decreased. In addition, the expression of TLR2/NF-κB in HaCaT cells was significantly reduced after CM treatment. On the other hand, an in vivo therapeutic effect of CM was assessed against M. globosa-infected mice. The fungal load on the skin decreased after treatment with CM compared to the M. globosa-infected group. In addition, the uninfected animals showed a normal skin structure, whereas, the M. globosa-infected mice showed extensive infiltration of neutrophils in skin tissues that improved after treatment with CM. Meanwhile, the levels of inflammatory and apoptotic factors improved after CM treatment. ConclusionOur results showed that CM inhibits the biofilm formation of M. globosa and eradicates mature biofilms of M. globosa. Treatment with CM significantly decreased oxidative stress, apoptosis, and inflammatory markers in the skin tissue and HaCaT cells. Hence, this study suggests that CM is a good candidate therapeutic agent against M. globosa-induced PV infections because of its antifungal, antibiofilm, and anti-inflammatory properties.

Oncomeric Profiles of microRNAs as New Therapeutic Targets for Treatment of Ewing's Sarcoma: A Composite Review.

Ewing's sarcoma is a rare type of cancer that forms in bones and soft tissues in the body, affecting mostly children and young adults. Current treatments for ES are limited to chemotherapy and/or radiation, followed by surgery. Recently, microRNAs have shown favourable results as latent diagnostic and prognostic biomarkers in various cancers. Furthermore, microRNAs have shown to be a good therapeutic agent due to their involvement in the dysregulation of various molecular pathways linked to tumour progression, invasion, angiogenesis, and metastasis. In this review, comprehensive data mining was employed to explore various microRNAs that might have therapeutic potential as target molecules in the treatment of ES.

Experimental and Theoretical Investigations on the Antibacterial Activity of Some Bromoaniline Compounds

Background: Test substrates are routinely used in laboratories to test the efficacy of various reactions, and while many substrates have found success as test substrates, not much is known about their potential intrinsic properties. On that note, some bromoaniline compounds were synthesized and repurposed by studying their antibacterial activity. Methods: The in-vitro antibacterial tests were done against S. aureus, K. pneumoniae, B. subtilis, and E. coli. Tests were carried out to understand the mode of action of the compounds where changes in permeability and integrity of cell membrane resulting in the leakage of UV absorbing materials were observed. Computational studies were performed by employing density functional theory (DFT) in the Gaussian09 software for determining the reactivity of the studied compounds. Molecular docking studies were executed to define the interaction of the synthesized compounds with microbial target proteins, Dihydrofolate reductase (PDB ID: 3SRW) and DNA gyrase subunit B (PDB ID: 1KZN). Results: The compound’s response to the mode of action tests showed alteration in the membrane permeability and its antimicrobial effectiveness at different pH contributed it to being a potential antibiotic. The results of DFT studies revealed that the molecular descriptors indicate better reactivity of compound 8b which is in agreement with the experiments performed. Molecular docking studies revealed that interactions of the compounds at the active sites of target proteins depict that the compounds are likely to bind to the protein enhancing their potential as antibacterial agents. Conclusions: This work concludes that simple molecules synthesized effortlessly through a simple and environmentally benign pathway, can pose as a good therapeutic agent

AuAg nanocomposites suppress biofilm-induced inflammation in human osteoblasts

Staphylococcus aureus (S. aureus) forms biofilm that causes periprosthetic joint infections and osteomyelitis (OM) which are the intractable health problems in clinics. The silver-containing nanoparticles (AgNPs) are antibacterial nanomaterials with less cytotoxicity than the classic Ag compounds. Likewise, gold nanoparticles (AuNPs) have also been demonstrated as excellent nanomaterials for medical applications. Previous studies have showed that both AgNPs and AuNPs have anti-microbial or anti-inflammatory properties. We have developed a novel green chemistry that could generate the AuAg nanocomposites, through the reduction of tannic acid (TNA). The bioactivity of the nanocomposites was investigated in S. aureus biofilm-exposed human osteoblast cells (hFOB1.19). The current synthesis method is a simple, low-cost, eco-friendly, and green chemistry approach. Our results showed that the AuAg nanocomposites were biocompatible with low cell toxicity, and did not induce cell apoptosis nor necrosis in hFOB1.19 cells. Moreover, AuAg nanocomposites could effectively inhibited the accumulation of reactive oxygen species (ROS) in mitochondria and in rest of cellular compartments after exposing to bacterial biofilm (by reducing 0.78, 0.77-fold in the cell and mitochondria, respectively). AuAg nanocomposites also suppressed ROS-triggered inflammatory protein expression via MAPKs and Akt pathways. The current data suggest that AuAg nanocomposites have the potential to be a good therapeutic agent in treating inflammation in bacteria-infected bone diseases.

Oil Extract of Momordica charantia Seed (OEMCS) Exhibits Biphasic Effect on Blood Coagulation, Antiplatelet and Antioxidant Properties

Aim: Extraction of Oil from Momordica charantia seed and its characterization. Materials and Methods: Oil was extracted from the dried seeds of Momordica charantia using Soxhlet apparatus with petroleum as a solvent at the temperature of 60°C for about 8 hr. Momordica charantia seed oil was characterized using GC-MS. anticoagulant, antiplatelet, and antioxidant assay toxicity studies were carried out. Results: The fatty acid profile obtained from GCMS suggested the presence of lipids at a fair percentage. (Saturated fats-38.67%, unsaturated fats-59.39% (MUFA- 1.56% and PUFA-57.83). The iodine value of extracted fatty acid was found to be 66.7 with a refractive index of 1.493 at 40°C. OEMCS exhibited a biphasic effect on plasma recalcification time. OEMCS showed a strong procoagulant effect at volume 1 to 10 μg by decreasing the clotting time from control 291 to 33sec. However, as the volume of oil was increased above 10μg it drastically shifted from pro-coagulation to anticoagulation by increasing the clotting time from 194 sec to 267 sec. Furthermore, the effect of OEMCS oil on platelet aggregation was analyzed using agonists such as ADP and epinephrine. Interestingly, OEMCS oil showed 44% and 97% platelet aggregation inhibition for ADP and Epinephrine in platelet-rich plasma. The antioxidant property of oil extract was tested by DPPH and LPO assays, OEMCS oil showed bleaching of DPPH absorption, reflecting on proton donating ability, and thereby free radical scavenging ability was confirmed. OEMCS decreased by 80% lipid peroxidation when compared with NaNo2-treated PRP alone at the highest dose of 150μg. OEMCS did not cause hemolysis to RBC, hemorrhage, and edema in experimental animals revealing its non-toxic nature. Conclusion: OEMCS exhibits a biphasic effect on plasma coagulation but shows strong antiplatelet and antioxidant activities. Meanwhile, it revealed non-toxic properties, thus OEMCS may prove to be a good natural therapeutic agent in oxidative stress and cardiovascular disorders.

Atividade inibitória in vitro de óleos essenciais derivados de especiarias para Aspergillus fumigatus multirresistente obtido de ração de aves

ABSTRACT Aspergillus fumigatus is a respiratory pathogen, which has the potential to cause brooder pneumonia in poultry chicks and aspergillosis in birds and farmers. Frequent and irrational use of antifungals has led to the development of resistance in the fungal species. The present study aimed to evaluate the antifungal activity of essential oils (EOs) from four different spices against multi-drug resistant (MDR) A. fumigatus isolated from 40 poultry feed samples. Twenty fungal isolates were identified to be A. fumigatus based on the macroscopic and microscopic characteristics, which were confirmed by targeting and amplifying the species-specific rodA gene (313 bp). Five (5/20) isolates were found to be MDR by the disk diffusion method. EOs were tested as an alternative strategy for 5 MDR isolates of A. fumigatus. Clove EO provided better activity by 6 log10 reduction for 30-90 min exposure as compared to other EOs, therefore, shortlisted for well-diffusion and minimum inhibitory concentration (MIC) method. Clove EO provided promising results as compared to fluconazole, amphotericin B, ketoconazole, nystatin and voriconazole as its mean ZOI (39.6 ± 6.34) were better than all other commercial antifungals (p< 0.001). Mean MIC was reported to be 0.195 ± 0.11 µl/ml. Safety testing of the EO produced 74-82% cell viability for the range of 0.390 - 0.097 µl/ml as compared to DMSO. Findings of the present study highlight that clove EO can be source of a good therapeutic agent for infections of MDR isolates of A. fumigatus.

Green synthesis and characterization of copper nanoparticles using Phragmanthera austroarabica extract and their biological/environmental applications

In the current scenario, the use of phytochemicals from the extracts of plants has become a unique approach for the biosynthesis of metallic nanoparticles because of their dual nature of capping and as reducing agents for the metallic nanoparticles. The current work describes a green method for the biosynthesis of copper nanoparticles (CuNPs) using extract of Phragmanthera austroarabica (P. austroarabica). The conditions of green synthesis were optimized to produce ideal size range for CuNPs. CuNPs were observed to have spherical and crystalline nature with particle size of 44.6 ± 2.7 nm, as confirmed by XRD, SEM, and TEM results. The fluorescence technique demonstrated that CuNPs are highly efficient probes for the detection of hexavalent chromium ions (Cr (VI)), with a limit of detection (LOD) of 1.20 nM, which is one of the lowest LODs reported for sensing substances. The CuNPs also exhibited excellent degradation efficiency for the industrial organic dyes, i.e., congo red (95.75% removal in 7 min) and methylene blue (96.67% removal in 11 min) with rate constants of 0.4829 and 0.3276 min−1, respectively. Furthermore, the results indicated that the CuNPs have high antioxidant activity. The cytotoxicity assay on human breast cancer cells (MDA-MB-231) also showed that CuNPs inhibited the growth of MDA-MB-231 cells with a half maximal inhibitory concentration (IC50) of 66.74 μg/mL, suggesting that the biosynthesized CuNPs may be a good potential therapeutic agent for human breast cancer treatment. CuNPs showed highly efficient antibacterial and antifungal effects against Staphylococcus aureus, Escherichia coli, Penicillium chrysogenum and Fusarium oxysporum. This is the first work reported on P. austroarabica plant mediated biosynthesis of CuNPs, and we believe that these results may pave the way for a new direction in the field of nanotechnology and nanomedicine. Hence, CuNPs may be potent agents in various environmental and biomedical applications that are yet to be explored in near future.

The Role of Systemic and Topical Beta-Blockers in Dermatology: A Systematic Review.

Beta-blockers are proven to be safe and cost-effective agents in treating multiple dermatological conditions, which is why they are considered as an interesting and good alternative therapeutic agent by dermatologists. To our knowledge, there has been no comprehensive systematic review to date summarizing the role of both systemic and topical beta-blockers in dermatology. In this systematic review, we aim to review recent and relevant published literature in order to provide a comprehensive evidence-based summary to inform dermatologists. An electronic-based literature search was carried out during October-December 2021 in the databases PubMed (MEDLINE), SCOPUS (EMBASE), and Cochrane Library. Furthermore, bibliographic sources were also reviewed for the selected articles. We followed The Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 (PRISMA) guidelines. We reviewed published literature about the role of beta-blockers in dermatology for the time period (January 2016 to December 2021). A total of 126 publications were retrieved from different databases, of which 59 studies were finally included in our review after excluding non-eligible literature in accordance with our inclusion and exclusion criteria. The included articles consisted of meta-analyses, systematic reviews, clinical trials, retrospective and prospective cohort studies, case-control studies, case series, and case reports. In general, data in reviewed literature showed that both systemic and topical beta-blockers were reliable and safe therapeutic options in treating different dermatoses. Their effect has been studied as a mono-therapy, also as an adjuvant therapy combined with other current disease-specific therapeutic modalities such as lasers, radiation, chemotherapy, corticosteroids, or other beta-blockers options. Local and systemic adverse effects were mainly minor and non-significant.

Extraction of Bioactive Compounds for Antioxidant, Antimicrobial, and Antidiabetic Applications.

This study was designed to check the potential of secondary metabolites of the selected plants; Citrullus colocynthis, Solanum nigrum, Solanum surattense, Calotropis procera, Agave americana, and Anagallis arvensis for antioxidant, antibacterial, antifungal, and antidiabetic agents. Plant material was soaked in ethanol/methanol to get the crude extract, which was further partitioned via solvent extraction technique. GCMS and FTIR analytical techniques were applied to check the compounds responsible for causing antioxidant, antimicrobial, and antidiabetic activities. It was concluded that about 80% of studied extracts/fractions were active against α-amylase, ranging from 43 to 96%. The highest activity (96.63%) was exhibited by butanol fractions of A. arvensis while the least response (43.65%) was shown by the aqueous fraction of C. colocynthis and the methanol fraction of fruit of S. surattense. The highest antioxidant activity was shown by the ethyl acetate fraction of Anagallis arvensis (78.1%), while aqueous as well as n-hexane fractions are the least active throughout the assay. Results showed that all tested plants can be an excellent source of natural products with potential antimicrobial, antioxidant, and antidiabetic potential. The biological response of these species is depicted as a good therapeutic agent, and, in the future, it can be encapsulated for drug discovery.

Superoxide Dismutase (SOD): A Promising Enzyme in the Area of Biopharmaceuticals in Its Native and Immobilized Form: A Review

Abstract: Super Oxide Dismutase (SOD) an ubiquitous potent antioxidant enzyme primarily scavenges reactive oxygen species (ROS) like superoxide radicals, which causes oxidative damage to a living organism’s essential proteins, lipids and its DNA. The accumulation of ROS in the body is a major inductive factor aging related diseases. It is important to maintain ROS at an appropriate level to prevent these diseases. SOD is a vital enzyme in defending against oxidative damage in vivo. The SOD enzyme promises to be a good therapeutic agent against ROS. The present review describes the therapeutic effects of SOD in some physiological and pathological conditions. Because of the defects in the direct application of SOD or SOD mimics, different mounting delivery systems (immobilization enzyme systems) have been developed for the efficient applications of SOD to realize antioxidant treatment.

Novel gold-platinum nanoparticles serve as broad-spectrum antioxidants for attenuating ischemia reperfusion injury of the kidney

Kidney ischemia reperfusion injury (IRI) is a common and inevitable pathological condition in routine urological practices, especially during transplantation. Severe kidney IRI may even induce systemic damage to peripheral organs, and lead to multisystem organ failure. However, no standard clinical treatment option is currently available. It has been reported that kidney IRI is predominantly associated with abnormally increased endogenous reactive oxygen species (ROS). Scavenging excessive ROS may reduce the damage caused by oxidative stress and subsequently alleviate kidney IRI. Here, we reported a simple and efficient one-step synthesis of gold-platinum nanoparticles (AuPt NPs) with a gold core having a loose and branched outer platinum shell with superior ROS scavenging capacity to possibly treat kidney IRI. These AuPt NPs exhibited multiple enzyme-like anti-oxidative properties simultaneously possessing catalase- and peroxidase-like activity. These particles showed excellent cell protective capability, and alleviated kidney IRI both invitro and invivo without obvious toxicity, by suppressing cell apoptosis, inflammatory cytokine release, and inflammasome formation. Meanwhile, AuPt NPs also had an effect on inhibiting the transition to chronic kidney disease by reducing kidney fibrosis in the long term. Thus, AuPt NPs might be a good therapeutic agent for kidney IRI management and may be helpful for the development of clinical treatments for kidney IRI.

Evaluation of betulinic acid effects on pain, memory, anxiety, catalepsy, and oxidative stress in animal model of Parkinson's disease.

Parkinson's disease (PD) is known for motor impairments. Betulinic acid (BA) is a natural compound with antioxidant activity. The present study addresses the question of whether BA affects motor and non-motor dysfunctions and molecular changes in the rat model of PD. The right medial forebrain bundle was lesioned by injection of 6-hydroxydopamine in Male Wistar rats (10-12weeks old, 270-320g). Animals were divided into Sham, PD, 3 treated groups with BA (0.5, 5, and 10mg/kg, IP), and a positive control group received L-dopa (20mg/kg, P.O) for 7days. rigidity, anxiety, analgesia, and memory were assessed by bar test, open-field, elevated plus-maze (EPM), tail-flick, and shuttle box. Additionally, the malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, Brain-derived neurotrophic factor (BDNF) and Interleukin 10 (IL10) levels in the whole brain were measured. BA significantly reversed the 6-hydroxydopamine-induced motor and memory complication in the bar test and shuttle box. It modified anxiety-like behavior neither in open-field nor in EPM. It only decreased the time spent in open arms. Moreover, no significant changes were found in the tail-flick between treatment and sham groups. On the other hand, the level of MDA & IL10 were decreased, while the activity of GPx levels of SOD & BDNF in the rats' brains was increased. Our results showed that BA as a free radical scavenger can account for a possible promise as a good therapeutic agent for motor and non-motor complications in PD however further studies may be needed.

Abstract 818: New targets in prostate cancer: Nuclear localization of galectin-1 in androgen receptor indifferent prostate cancer

Abstract Currently, no morphological characteristics have been described in clinical specimens to delineate an androgen receptor (AR)-active from an AR-inactive phenotype in AR-expressing aggressive variant prostate cancer (AVPC). 36 localized and 51 metastatic prostate cancer (CaP) samples were analyzed - 19 (37.3%) of the metastases were in the bone, 20 (39.2%) were in the lung, while the rest were in other areas such as brain, lymph node, bladder, etc). Expression level of Gal-1 was graded individually in the nucleus and the cytoplasm of both primary and metastatic tissues. Very low Gal-1 expression was observed in epithelial cells of benign prostate, while stromal staining was strong. Localized prostate tumors obtained from prostatectomy samples showed strong gal-1 expression in the epithelial cells, but remarkably the Gal-1 staining was confined to the cytoplasm. In contrast, in metastatic tumors many nuclei stained for Gal-1. Among localized tumors, Kaplan-Meier curves showed a significant increase in metastasis formation (p=0.022) and decreased overall survival (p=0.015) among those expressing nuclear Gal-1 (n=16) compared to those with no nuclear Gal-1 (n=20). Whereas cytoplasmic Gal-1 negatively correlated with patient age (R=-0.51, p=0.008) and PSA (R=-0.41, p=0.006), and positively correlated with Ki67 (R=0.35, p=0.014), the expression of nuclear Gal-1 correlated strongly with the expression of NE markers including chromogranin A (R=0.32, p=0.031). Significantly, nuclear Gal-1 was expressed in AVPC models but not in those derived from localized tissues. Significantly, androgen deprivation, including treatment with AR antagonists, resulted in nuclear localization of Gal-1. We adapted the powerful one-bead-two-compound (OB2C) combinatorial library method for the discovery of synthetic small molecule death ligands against cancer cells in an ultra-high throughput fashion. One of these benzimidazole-based ligands, LLS80, was active against tumor cells at low micromolar IC50. Pull-down assay followed by LC MS/MS indicated that galectin-1 is the target protein of LLS80, which induced apoptosis preferentially in AVPC cells expressing high level of Gal-1. LLS80 has all the indicators of being a good therapeutic agent: (i) LLS80 has a low in vitro IC50 in AVPC cells, (ii) it shows significant in vivo anti-tumor efficacy using xenograft models, (iii) it is a novel small molecule that can penetrate AVPC cells, (iv) it can synergize with enzalutamide in vivo and in vitro, (v) it inhibits a known therapeutic target, Gal-1, and (vi) low toxicity. Treatment with LLS80 (2 µM) prevented AR antagonist-induced Gal-1 nuclear localization, and also downregulated NE markers in AVPC models of CaP progression. We conclude that nuclear Gal-1 is a novel marker of AVPC. Citation Format: Maria Malvina Tsamouri, Salma Siddiqui, Blythe P. Durbin-Johnson, Kit S. Lam, Ruiwu Liu, Paramita M. Ghosh. New targets in prostate cancer: Nuclear localization of galectin-1 in androgen receptor indifferent prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 818.

SILVER DIAMINE FLUORIDE - A REVIEW

Despite the fact that the prevalence and severity of dental caries in children has decreased in recent decades, children from low socioeconomic backgrounds continue to endure the consequences of dental caries in many developed and developing nations. The antibacterial action of silver compounds has been demonstrated through the use of silver compounds for the prevention and treatment of various infections for over a century. Though silver diamine fluoride (SDF) was used to prevent dental cavities in Japan throughout the 1970s, it was little known in the rest of the globe. A 38 percent (44,800 ppm fluoride) SDF solution is now widely used in several countries to prevent cavities and relieve hypersensitivity in primary and permanent teeth. SDF application to prevent dental cavities is a non-invasive, rapid, and uncomplicated technique. According to reports from published studies, SDF application did not cause serious pulpal damage. It does, however, have some disadvantages, such as black darkening of carious teeth and an unpleasant metallic taste. However, due to its low cost and ease of usage, SDF appears to be a good therapeutic agent for use in community dental health projects.

EFFECTS OF EXTRACELLULAR VESICLES ISOLATED FROM SUBVENTRICULAR ZONE ON MOLECULAR CHANGES FOLLOWING SPINAL CORD INJURY ON WISTAR RATS

Spinal cord injury (SCI) may occur as a result of traumatic crash to the spine that dislocates one or many vertebrae. SCI has two events to bring about the injury in the spinal cord that result at the end it will lead to bad consequences and loss of neurons; SCI complications are general loss of motor and sensory function. Extracellular vesicles (EVs) are very small vesicles produced by cells that contribute to cell to cell communication, transferring bioactive lipids, proteins, RNA. The aim of this research is to determine the effect of EVs on inflammasomes complex after SCI on rats. EVs were harvested characterized and cultured as exosomes, the animals are divided to 5 groups: control, sham, vehicle, SCI + treatment, SCI + EVs group. Spinal cord injury was induced using weight compression. 10 μl of EVs were injected intrathecally into lumber cistern in a space between L4-L5 laminae slowly. Gene expression of Caspase-1, ASC and NLRP3 were determined by RT-PCR. Western blot for determining the protein content of the inflammasomes were carried out. SCI up regulated the level of inflammasome complex both mRNA and proteins. Inthrathecal injection of EVs down regulated the inflammasome complex and make neuronal recovery. SCI can up regulate the level of inflammasome complex both mRNA and proteins. EVs are good therapeutic agent for SCI and increase neuronal recovery, inthrathecal injection is the best method of injection MSCs for treatment of SCI.

Human Cryptic Host Defence Peptide GVF27 Exhibits Anti-Infective Properties against Biofilm Forming Members of the Burkholderia cepacia Complex.

Therapeutic solutions to counter Burkholderia cepacia complex (Bcc) bacteria are challenging due to their intrinsically high level of antibiotic resistance. Bcc organisms display a variety of potential virulence factors, have a distinct lipopolysaccharide naturally implicated in antimicrobial resistance. and are able to form biofilms, which may further protect them from both host defence peptides (HDPs) and antibiotics. Here, we report the promising anti-biofilm and immunomodulatory activities of human HDP GVF27 on two of the most clinically relevant Bcc members, Burkholderia multivorans and Burkholderia cenocepacia. The effects of synthetic and labelled GVF27 were tested on B. cenocepacia and B. multivorans biofilms, at three different stages of formation, by confocal laser scanning microscopy (CLSM). Assays on bacterial cultures and on human monocytes challenged with B. cenocepacia LPS were also performed. GVF27 exerts, at different stages of formation, anti-biofilm effects towards both Bcc strains, a significant propensity to function in combination with ciprofloxacin, a relevant affinity for LPSs isolated from B. cenocepacia as well as a good propensity to mitigate the release of pro-inflammatory cytokines in human cells pre-treated with the same endotoxin. Overall, all these findings contribute to the elucidation of the main features that a good therapeutic agent directed against these extremely leathery biofilm-forming bacteria should possess.