Poisoning Research Articles

Cleistopholis patens root bark extract exerts cardioprotective effect against doxorubicin-induced myocardial toxicity in rats

Abstract Background Myocardial Infarction still persists as the most prevalent cardiovascular disease and is a top cause of morbidity and mortality in doxorubicin treated cancer patients. This study evaluated the prophylactic effect of the ethanol root bark extract of Cleistopholis patens (ERBECP) against doxorubicin-induced myocardial infarction in wistar rats. Extraction, preliminary phytochemical analysis, acute toxicity study and body weight (b.w.) of ERBECP were achieved using standard methods. Phyto-constituents in ERBECP were indentified using Gas Chromatography-Mass Spectrometry (GC–MS) technique. Thirty (30) male albino Wistar rats of average b.w. ranging between 100 and 130 g were divided into six groups of five rats each. Groups I, II and III served as normal, doxorubicin (DOX) and standard (Vasoprin 150 mg/kg b.w) controls respectively, while groups IV, V and VI were orally pre-treated with the extract (200, 400 and 600 mg/kgb.w) for two weeks prior to intraperitoneal induction of cardiotoxicity with DOX (20 mg/kg bw) on day 14. Results Disturbances in serum cardiac function bio-markers such as; Cardiac Troponin-I (CTnI), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT). Lipid profile markers such as; Total cholesterol (TC), Triacylglycerol (TAG), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL). Oxidative stress markers such as; Malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH) confirmed the induction of myocardial infarction. Histological assessment of heart tissues was performed to validate biochemical results. The GC–MS analysis of ERBECP identified a total of 69 compounds. Safety profile of the aqueous extract was safe for the animals up to the highest dose of 5000 mg/kg b.w. Pre-treatment of DOX group with ERBECP could significantly increase the b.w. compared to the DOX-treated group during the experimental period of 2 weeks. There were significant (p < 0.05) alterations in the levels of CTnI, CK, LDH, AST, ALT and lipid profile indices in the DOX control rats. Also, significant (p < 0.05) increase was observed in MDA and decrease in SOD, CAT and GSH in the DOX control rats. However, administration of the extract significantly (p < 0.05) normalized these alterations and reversed the architectural changes in the heart. The 69 compounds were screened against the target protein (CBR1); we identified seven hits based on the docking score and interactions with the active site residues. All the C. patens constituents had MW (g/mol) less than 500, HBA < 10 and HBD not more than 5. Apart, 9-Octadecenoic acid (Z)-, 2,3-dihydroxy propyl ester and Estra-1,3,5(10)-trien-17. beta. -ol, all the constituents had LD50 lower than 2000 mg/kg. Conclusions The findings reveals ERBECP demonstrated promising potential and can be exploited in the development novel cardiac therapeutic agents.

Clinical Pharmacology of Cytokine Release Syndrome with T-cell Engaging Bispecific Antibodies: Current Insights and Drug Development Strategies

Abstract Cytokine release syndrome (CRS) is a common acute toxicity in T-cell therapies, including T-cell engaging bispecific antibodies (T-BiSp). Effective CRS management and prevention is crucial in T-BiSp development. Required hospitalization for 7 of the 9 approved T-BiSp and the need for clinical intervention in severe cases highlight the importance of mitigation strategies to reduce healthcare burden and improve patient outcome. In this review, we discuss the emerging evidence on CRS mitigation, management, and prediction. We cover different strategies for dose optimization, current and emerging (pre)treatment strategies, quantitative pharmacology tools employed during drug development, and biomarkers and predictive factors. Insights are gleaned on step-up dosing and formulation effects on CRS and CRS relationships with cytokine dynamics and drug levels gathered through review of T-BiSp licensing applications and emerging data from conferences and publications.

Anti- Inflammatory Activities Of The Methanol Leaf Extract And Fractions Of Elaesis Guineensis In In-Vivo Animals

Abstract Objective Objective of this paper is to investigate the preliminary anti-inflammatory property of the leaves and its fractions of Elaesis guineensis using egg induced albumin and formaldehyde induced arthritis models in rats. Method Egg albumin induced inflammation was induced by sub-plantar injection of 0.1 ml of fresh undiluted egg albumin. The volume of distilled water displaced by the treated paw was measured at 0.5,1, 2, 3, 4, 5, and 6 hours after induction of inflammation. Formaldehyde-induced arthritis was induced after 30 min by sub-plantar injection of 0.1 ml of 2.5% formaldehyde solution and was repeated on day 3. Arthritis was assessed by measuring the volume of distilled water displaced by the paw before induction of arthritis and once every day for ten days, starting from day one, after induction of arthritis. Results The acute toxicity test revealed that the plant extract was safe even at 5000 mg/kg dose level. The methanol extract (ME) showed a dose-dependent inhibition of egg albumin-induced acute inflammation that peaked at the dose of 200 mg/kg, while the fractions of the extract showed that the hexane and ethyl acetate fractions had the highest activity during the experiment. Similarly, the crude extract of the formaldehyde induced arthritis showed a dose-dependent inhibition making the 200 mg/kg the most active dose level. Additionally, it was observed that among the fractions of the extract the hexane fraction (HF) showed the most significant inhibitory activity when compared to other fractions Conclusion this study establishes that the methanol leaf extract and fractions ofElaesis guineensis possess significant anti-inflammatory activity

Psychological outpatient follow-up after hospitalization for adolescent acute alcohol intoxication.

The findings of this study demonstrate that a preventive program following acute alcohol intoxication contributes to the reduction of adolescent alcohol use and associated risk-taking behaviours. • Earlier studies showed that adolescents with problematic alcohol use reported reduced alcohol consumption and fewer alcohol-related problems after participating in a motivational interviewing intervention compared to standard care. • During the follow-up assessment of adolescents with acute alcohol intoxication it is possible to signalize mental disorders and to determine whether the patient requires referral to specialized mental healthcare. • These findings suggest that the preventive program had a short-term impact in reducing alcohol consumption among adolescents with acute alcohol intoxication, as well as a long-term impact in reducing binge-drinking behaviours. • The program's success in mitigating binge-drinking behaviours aligns with its goals of promoting safer drinking habits among adolescents.

Nurses’ reported training needs for advanced cell therapies: a survey on behalf of the Nurses Group of the EBMT

Background Advanced Therapy Medicinal Products (ATMPs) for human use have advanced globally with the rapid adoption of Chimeric Antigen Receptor T-cell (CAR-T) therapies in haemato-oncology. CAR-T cell therapy and ATMPs have unique, significant acute and chronic toxicities, and appropriate patient care is crucial. Significant challenges, including the need for nurse education and training, accompany optimal patient success and benefits. Objectives This study aimed to describe nurses’ training needs in relation to ATMP management and patient care. Methods A cross-sectional online survey was performed by the European Society for Blood and Marrow Transplantation, based on a previously tested questionnaire developed in the UK. Findings 109 complete responses from 86 different centers from 24 countries were returned (1207 distributed). Over 1/3 reported experience delivering licensed ATMPs (CAR-T). High-priority training areas included a general introduction to ATMPs, toxicity management, product-specific information, and regulatory frameworks for ATMPs. A clear need for ATMP-specific training exists and is regarded as important. Training prior to implementation is key and should be supported by ongoing competency maintenance. Counseling, patient support, and long-term follow-up are identified for future training and opportunities for nurse experience sharing in this rapidly evolving field.

Proton beam therapy for craniopharyngioma: a systematic review and meta-analysis.

Craniopharyngioma is a rare and slow-growing benign sellar or parasellar epithelial tumor. The number of patients receiving proton beam therapy (PBT) has increased. This study aimed to systematically evaluate and analyze the comprehensive evidence regarding the safety and efficacy of PBT for craniopharyngioma. We searched four databases: the Cochrane Library, PubMed, Embase, and Web of Science. The period was from their inception to February 16, 2024. Two researchers independently screened the literature and extracted data. Among 486 candidate articles, eight studies were included in our study. Exactly 393 patients with craniopharyngioma underwent PBT in these studies. These studies reported data on survival and toxicity. The median sample size was 42.5 patients. The median age was9.1-37years; the female proportion was 48.9%, and the median follow-up time was 29-91.4months. All patients were treated once daily, five times a week, with a fraction of 1.8Gy (RBE) per session. The median total dose was 54.0Gy (RBE). The local control rates at 3 and 5years in these studies were 99% and 93%, respectively. The overall survival rates at 3 and 5years in these studies were both 100%. The incidence of acute and late toxicities was mainly grade 1-2. The main late toxicities included vascular and visual toxicities, hypothalamic obesity, endocrinopathy, and panhypopituitarism. PBT for craniopharyngioma, especially in children and adolescents, has shown impressive local control and acceptable acute and late toxicities.

Precipitate, preterm labor in acute organophosphate poisoning in pregnancy: A case report

Introduction: Acute organophosphorus poisoning (AOPP) during pregnancy is uncommon. When complicated by preterm labor, it presents therapeutic dilemmas due to the lack of established guidelines. Case Presentation: We describe a case of a 19-year-old primigravida at 33 weeks of gestation with AOPP. During her treatment, she unexpectedly experienced preterm, precipitate labor, resulting in the delivery of a live, healthy baby. Discussion: Late-pregnancy exposure to organophosphates may trigger preterm labor through receptor hyperstimulation from excess acetylcholine, causing premature contractions. Atropine, progesterone, and magnesium sulfate may help manage these effects. Conclusion: This case underscores the importance of vigilance and frequent clinical examinations in patients with AOPP to identify subtle early signs of potential complications.

Biofilm targeting with chitosan-based nanohydrogel containing Quercus infectoria G. Olivier extract against Streptococcus mutans: new formulations of a traditional natural product.

Biofilm formation has a crucial role in the cariogenic virulence of Streptococcus mutans, which leads to resistance to common antibacterials. The antimicrobial resistance crisis has led to increased research about traditional natural products. Quercus infectoria extract (QI extract) and nano hydrogels containing QI extract (QI-NH) and tannic acid (TA-NH) were evaluated against this pathogen. QI extract was analyzed by HPLC and the physiological characteristics of nanohydrogels were assessed by SEM, FTIR, zeta potential, DLS and determination of release kinetics and encapsulation efficiency. Determination of MIC and MBC of the material and their anti-biofilm effect was done by the microtiter method and on the extracted tooth surface. The properties of extracts and nano hydrogels in the expression of genes codifying glucosyltransferases (gtfB, gtfC and gtfD) and glucan binding protein B (gbpB) were quantified. Their toxicity was tested by the MTT method against the KB cell line. According to HPLC, 55.18% of QI extract contained TA. The encapsulation efficiency of QI-NH and TA-NH was equal to 60% and 80%, respectively. SEM and FTIR exhibited that QI extract and TA were successfully entrapped in the networks resulting from the chemical bonding of chitosan and TPP. The average size of QI-NH and TA-NH was 70.45 and 58.43nm, and their zeta potential was 6.17 ± 2.58 and 0.25 ± 0.03 mv, respectively. PDI < 0.3 of nano hydrogels indicated the favorable polydispersity of nanohydrogels. MIC of QI extract, QI-NH and TA-NH were 937.5, 30 and 10µg/ml, respectively. Also their MBIC50 was 35.1, 2.1 and 0.95µg/ml, respectively, and the extracts and nano hydrogels restrained the biofilm maturation on enamel. The pivotal genes of S. mutans in biofilm formation were significantly less expressed by treatment with QI-NH and TA-NH than others. Based on the MTT test, QI-NH had less acute toxicity than QI extract and TA-NH. IC50 of QI-NH was calculated as 775.4µg/ml, while it was equal to 3.12µg/ml for chlorhexidine as a common antibacterial agent. QI-NH, a new formulation derived from traditional anti-caries, can be a safe and efficient option to combat dental biofilm.

Toxicological evaluation of Carthamus lanatus L (Carthame laineux) hydro-alcoholic extract in Wistar rats: acute oral toxic effects

Background: Despite the well-known phytotherapeutic properties of Carthamus lanatus L in traditional medicine, there is little evidence on its toxicity profile in hematological and biochemical parameters. Objective: This study was intended to evaluate the acute toxicity effect of Carthamus lanatus L. Methods: The toxicological impact of a hydroalcholic extract of Carthamus lanatus (HAECL) at 200, 400, and 800 mg/kg body weight on hematological indices in rats was assessed gradually at 24 hours after 1, 10, and 14 days. Results: We observed no significant difference in the consumption of food, body weight, or relative organ weights. Hematological and biochemical parameters revealed the non-adverse effects of prolonged oral consumption of Carthamus lanatus except for a slight increase but no significant increase in ASAT and ALAT and a no significant decrease in the percentage of basophils. Conclusions: These data imply that the extract has a non-hematotoxic potential. Overall, the impact of carthamus lanatus extract in this study shows that it is unlikely to be hematotoxic and might be a promising candidate in the treatment of coronary heart disease if taken at the levels tested.

Interstitial HDR brachytherapy for anal cancer-results and quality of life.

While anal cancer is avery rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. Atotal of 96patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30v.3 and the specific QOL-ANL27 questionnaire. Local control was 85.5% at 5years, 83.4% at 10years, 83.4% at 15years, and 83.4% at 20years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to atoilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.

Study of anti-inflammatory activity and acute toxicity indicators of new silver salt of pyrazole-3-carboxamide

Objective. To study the anti-inflammatory activity and some toxicological indicators of the new derivative of pyrazole-3-carboxamide SSP. Materials and methods. To assess the biological activity of the compound, its anti-inflammatory effect was studied in the model of acute inflammatory edema caused by sub-plantar injection of carrageenan solution into a rat`s hind leg. The duration effect was assessed by the intensity of suppression of the inflammatory response in relation to the control level. In order to study the safety of the substance, the local irritant effect was determined when applied cutaneously in the experiments on rats. The severity of the irritant effect was assessed by the erythema degree, the amount of edema and the increase in local skin temperature. In addition, acute toxicity of the substance under study was determined. The test compound and reference drugs were applied to the skin. Results. The study of acute toxicity of the compound SSP and the reference drug nystatin when applied cutaneously to rats showed that LD50 of both substances was more than 2500,0 mg/kg. Indicators of the degree of local irritating effect of the drugs demonstrate its absence. At the same time, the studied SSP compound has no anti-inflammatory effect administered either orally or cutaneously. Conclusions. The data obtained allow us to classify the new silver salt of pyrazol-3-carboxamide SSP as a class 5 non-toxic substance. The studied SSP compound has no local irritant effect and does not demonstrate anti-inflammatory activity in the carrageenan inflammation model.

Long-term outcomes and prognostic factors of short-course radiotherapy (SCRT) in rectal cancer: a monocentric retrospective study.

To evaluate efficacy and tolerance of short-course radiotherapy (SCRT) prior to possible chemotherapy (CHT) and surgery in 64 patients with locally advanced rectal cancer, in terms of acute and early late toxicity and survival outcomes with prognostic factors. Sixty-four patients affected by rectal tumor were treated from 2008 to 2023 radiation therapy, with a total dose of 25Gy in 5 fractions. The Kaplan-Meier method was used to estimate the rates of overall survival (OS), cancer specific survival (CSS), local control (LC), disease free survival (DFS) and metastasis free survival (MFS). Univariate analysis for prognostic factors was performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios. Toxicity assessment has been considered in acute and in early late for gastrointestinal (GI), genitourinary (GU) districts. Median follow-up was 49.6months. The median OS was 65months with 1-year, 2-year and 5-year OS at 90.6%, 77.7% and 60% respectively. CSS at the 1-year, 2-year and 5-year was 98.3%, 96.2% and 86.2% respectively. LC at 1-year, 2-year and 5-year was 93.4%, 89.4% and 87.2% respectively. DFS at the 1-year, 2-year and 5-year was 93.4%, 89% and 87% respectively. The status of lymph nodes at diagnosis was a prognostic factor in term of LC and DFS. Acute GI toxicity was G1 in 10 (15.6%) patients. Five (7.8%) patients had a G1 acute GU toxicity. Fifteen (23.4%) patients developed chronic GI toxicities. SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

Efficacy of palliative hemostatic radiotherapy for tumor bleeding and pain relief in locally advanced pelvic gynecological malignancies.

The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains atherapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy. We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief. In total, 40patients with amedian planning target volume of 804 cm3 were treated with amedian total dose of 39 Gy in 13fractions, resulting in 6‑month and 1‑year local control rates of 66.9 and 60.8%, respectively. No higher-grade (>gradeIII) acute RT-induced toxicity appeared. Complete cessation of bleeding was achieved in 80.0% of all patients after amedian of 16days and pain relief was documented in 60.9% at first follow-up. 37.5% of the women required ablood transfusion and 25% an additional tamponade with local hemostatic agents. Successful stopping of bleeding was significantly less frequent in patients receiving anticoagulation concurrently with radiation and in the case of infield re-irradiation. Patients with ahigher total RT dose had cessation of bleeding significantly more often, with acut-off value of at least EQD2 (α/β = 10) = 36 Gy. The applied RT technique and planning target volume had no significant influence on the occurrence of bleeding cessation. Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in tumor bleeding and pain relief.

Evaluation of the potential anti-arthritic effects and evaluation of acute oral toxicity of the active fraction of Eclipta prostrata leaves in rat model

The primary goal of this research was to isolate and assess the bioactive compounds within Eclipta prostrata Linn’s chloroform extract, with a focus on their potential to combat arthritis, validating its traditional use. Initially, antioxidant characteristics were evaluated, followed by fractionation through column chromatography. The in-vivo safety assessment, following OECD TG 425 Guidelines, showed no mortality at doses up to 2000 mg/kg, confirming the fraction’s safety. Subsequently, the active fraction was assessed in a complete Freund’s adjuvant-induced arthritis model. It demonstrated a dose-dependent inhibitory effect on inflammation and improved various parameters, including thermal latency time, dorsal flexion, motility, and motor coordination. Active bio constituents like rutin, stigmasterol, quercetin, and beta-sitosterol were estimated in the active fraction. The findings provide validation for the traditional use of E. prostrata as a potential plant with anti-arthritic properties, suggesting its potential suitability for rheumatoid arthritis treatment.

5'-Noraristeromycin Repurposing: Well-known S-Adenosyl-L-homocysteine Hydrolase Inhibitor As a Potential Drug Against Leukemia

5ˊ-Noraristeromycin as a racemic mixture of enantiomers was found to exhibit a pronounced cytotoxic effect on leukemia cells; IC50 for the Jurkat, K562, and THP-1 cell lines was 7.3, 1.3, and 3.7 μM, respectively. The general toxicity of 5'-noraristeromycin was studied in experiments on white mice upon single-dose intragastric administration; toxicometric parameters were determined, and the clinical and pathomorphological presentation of acute intoxication was studied. LD50 of the substance was shown to be 63.2 (52.7÷75.8) mg/kg; LD16, 44.7 mg/kg, and LD84, 89.4 mg/kg. Administration of the substance at a dose within the studied dose range is accompanied by systemic damage to the internal organs and tissues of the experimental animals.

Preparation and anti-colon cancer effect of a novel curcumin analogue (CA8): in vivo and in vitro evaluation

Chemotherapy remains the first choice of treatment for colon cancer despite the inevitable adverse effects. Curcumin (CU) possesses antitumor activity but has poor aqueous solubility, low bioavailability, and weak activity. To address this, nine novel monocarbonyl CU analogues were designed, synthesized, and evaluated in the present study. Among them, CA8 exhibited the highest water solubility, which was approximately 2.37 × 106 times that of CU. In addition, compared with CU, its cytotoxicity on Caco-2 cells (19.2 times/48 h) was stronger. Of note, CA8 arrestedthe cell cycle of Caco-2 cells at the G2/M phase and induced apoptosis. Meanwhile, acute toxicity experiments indicated that KM mice tolerated CA8 for up to 300 mg/kg CA8 (oral administration) and 50 mg/kg CA8 (intraperitoneal injection). The oral administration of CA8 to Sprague Dawley rats exhibited higher AUC (0-t) (6.23-fold) and longer MRT (0-t) (3.35-fold) than that of CU. CA8 also inhibited the proliferation and angiogenesis of tumor cells more than CU and tegafur. Finally, CA8 may exert anti-tumor effects through the activation of JNK pathway and inhibition of AKT pathway. These results suggest that CA8 is a safe and highly effective new drug for colon cancer treatment.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.

The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action.

Antitumor Effect of Peptide-Camptothecin Conjugate Targeting CD133 Protein.

The peptide-drug conjugate (PDC) has emerged as one of the new approaches for cancer therapy, which has the advantages of improved drug target ability and reduced adverse effects compared with the traditional chemotherapy. CD133 is a surface antigen specific to cancer stem cells, which are thought to be responsible for the self-renewal, proliferation, metastasis, and chemoresistance of cancer cells. A PDC for CD133 was designed by us, and it consists of CD133 targeting peptide LS-7 (amino acid sequence LQNAPRS), a pH-sensitive linker (succinyl), and a cytotoxic payload, the cytotoxic molecule camptothecin (CPT) with potent toxicity in vivo and in vitro. An antitumor study exhibited that the conjugate LS-7-CPT has not only improved its cytotoxicity in tumor cells but also retained its anticancer effect in vivo. In addition, the acute toxicity in mice of LS-7-CPT has been improved and the maximum tolerated dose has been increased by at least 56.2-fold. Pull-down and in vivo fluorescent imaging results indicated that LS-7-CPT was enriched in mice tumors by targeting CD133 protein. As far as we know, this is the first report for a PDC molecule designed for CD133, which is important for the study of CPT drug development.

Screening of Cholinoreceptor Agonists in Experimental Model on Daphnia magna Straus

The acute toxicity and the ability of cholinoreceptor agonists to induce atypical motor hyperactivity in zoohydrobionts Daphnia magna Straus, equivalent to a significant seizure state in warm-blooded animals, were evaluated. Determination of this test function may be useful in screening assessment of pharmacological activity of cholinergic substances.