Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects. METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects. CONCLUSIONS: This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

Severe febrile neutropenia and pancytopenia in a patient with advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab: a case report.

Background: Immune checkpoint inhibitors (ICIs), agents that stimulate T-cell function, have become the standard first-line treatment for unresectable hepatocellular carcinoma (HCC). However, they may also cause immune-related adverse events (irAEs), which are rare and have not been extensively reported. Here, we describe a case of severe febrile neutropenia and pancytopenia after atezolizumab plus bevacizumab (atezo/bev) therapy and its treatment course. Case Description: The combination of atezo/bev was initiated as the first-line treatment for a man in his early 50s, who was diagnosed with unresectable HCC. The first treatment cycle was administered in the outpatient setting, and the patient developed a fever of 39.0 ℃ 10 days after therapy initiation. He presented 5 days later with persistent fever as well as a headache, vomiting, chills, generalized pain, fatigue, mild abdominal discomfort, and a burning rash present on his neck and face. Complete blood counts showed severe neutropenia [absolute neutrophil count (ANC) of 90 cells/µL], leukopenia [white blood cell (WBC) count 500 cells/µL], thrombocytopenia [platelet count (PC) 18,000 cells/µL], and mild anemia (hemoglobin level 12.6 gm/dL). Imaging findings showed colitis on computed tomography (CT). Atezo/bev therapy was discontinued. Treatment plan constituted of cefepime and filgrastim, a recombinant form of the naturally occurring granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia, metronidazole for colitis, and intravenous methylprednisolone for immune-related toxicities. The patient fully recovered after 4 days of admission. Conclusions: In conclusion, we observed temporary severe febrile neutropenia and pancytopenia during systemic immunotherapy in a patient with unresectable HCC. Healthcare providers should consider hematological irAEs (hem-irAEs) in patients after the administration of ICIs.

The preventive effects of diosmin alone or combined with irinotecan on 1,2-dimethylhydrazine-induced colon cancer in rats.

OBJECTIVE: Colorectal cancer, one of the most frequently diagnosed cancers worldwide, has a high mortality rate. Thus, our research aims to examine the preventive effects of diosmin (DIO) alone and in conjunction with the anti-cancer drug irinotecan (camptothecin-11, CPT-11), on 1,2-dimethylhydrazine (DMH)-induced colon cancer (CC) in male Wistar rats. MATERIALS AND METHODS: Fifty adult male Wistar rats were categorized into five groups. Group I (Normal) received saline 0.9 orally % as a vehicle once a week for 14 weeks. Group II (DMH) received DMH (20 mg/kg/week) orally dissolved in 0.9% saline for 14 weeks and 1% carboxymethylcellulose (CMC) every other day for the final 10 weeks. Group III (DMH+DIO) received DMH orally for 14 weeks and DIO (10 mg/kg, suspended in 1% CMC) every other day for the final 10 weeks. Group IV (DMH+CPT-11) received DMH orally for 14 weeks and intraperitoneal injection of CPT-11 (3 mg/kg) twice a week for the final 10 weeks. Group V (DMH+DIO+CPT-11) orally received DMH for 14 weeks and both DIO and CPT-11. RESULTS: All treated groups showed a significant reduction (p<0.05) in their elevated serum malondialdehyde levels and significant amelioration (p<0.05) of their lowered activities of colon glutathione-S-transferase (GST) and glutathione reductase (GR) as well as serum glutathione level (GSH). In addition, simultaneous treatment with DIO and CPT-11 led to a significant decrease (p<0.05) in the elevated serum levels of carcinoembryonic antigen (CEA) in rats administered with DMH, as well as a reduction in the colon expression levels of the inflammatory mediator (NF-κB), cell proliferator protein (Ki-67), and proapoptotic protein (p53). CONCLUSIONS: These findings suggest DIO, CPT-11, and their combination have anticarcinogenic effects against DMH-induced CC by suppressing oxidative stress, simulating the antioxidant defense system, attenuating the inflammatory effects, and reducing cell proliferation.

SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147.

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While lymphocytosis indicates an active anti-viral response, lymphopenia is a sign of poor prognosis. T-cells, in essence, rarely express ACE2 receptors, making the cause of cell depletion enigmatic. Moreover, emerging strains posed an immunological challenge, potentially alarming for the next pandemic. Herein, we review how possible indirect and direct key mechanisms could contribute to SARS-CoV-2-associated-lymphopenia. The fundamental mechanism is the inflammatory cytokine storm elicited by viral infection, which alters the host cell metabolism into a more acidic state. This "hyperlactic acidemia" together with the cytokine storm suppresses T-cell proliferation and triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results in a shift from steady-state hematopoiesis to stress hematopoiesis. Even with low ACE2 expression, the presence of cholesterol-rich lipid rafts on activated T-cells may enhance viral entry and syncytia formation. Finally, direct viral infection of lymphocytes may indicate the participation of other receptors or auxiliary proteins on T-cells, that can work alone or in concert with other mechanisms. Therefore, we address the role of CD147-a novel route-for SARS-CoV-2 and its new variants. CD147 is not only expressed on T-cells, but it also interacts with other co-partners to orchestrate various biological processes. Given these features, CD147 is an appealing candidate for viral pathogenicity. Understanding the molecular and cellular mechanisms behind SARS-CoV-2-associated-lymphopenia will aid in the discovery of potential therapeutic targets to improve the resilience of our immune system against this rapidly evolving virus.

Genomic Biomarkers to Predict Response to Atezolizumab Plus Bevacizumab Immunotherapy in Hepatocellular Carcinoma: Insights from the IMbrave150 Trial.

Introduction: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of anti-tumor macrophages and activated T-cells, potentially explaining its better response. Conclusions: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Mucosal immunization with ChAd-SARS-CoV-2-S prevents sequential transmission of SARS-CoV-2 to unvaccinated hamsters.

COVID-19 vaccines have successfully reduced severe disease and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, COVID-19 vaccines are variably effective in preventing transmission and symptomatic SARS-CoV-2 infection. Here, we evaluated the impact of mucosal or intramuscular vaccine immunization on airborne infection and transmission of SARS-CoV-2 in Syrian hamsters. Immunization of the primary contact hamsters with a mucosal chimpanzee adenoviral-vectored vaccine (ChAd-CoV-2-S), but not intramuscular messenger RNA (mRNA) vaccine, reduced infectious virus titers ~100-fold and 100,000-fold in the upper and lower respiratory tract of the primary contact hamster following SARS-CoV-2 exposure. This reduction in virus titer in the mucosal immunized contact animals was sufficient to eliminate subsequent transmission to vaccinated and unvaccinated hamsters. In contrast, sequential transmission occurred after systemic immunization with the mRNA vaccine. Thus, immunization with a mucosal COVID-19 vaccine protects against cycles of respiratory transmission of SARS-CoV-2 and can potentially limit the community spread of the virus.

Catalytic reduction of toxic dyes over nickel oxide nanoparticles supported on CMK-3 catalyst.

In the current paper, a NiO nanoparticles-loaded mesoporous carbon (CMK-3) catalyst, denoted as NiO/CMK-3, has been successfully synthesized using a facile strategy. The as-prepared material has been characterized through XRD, Raman spectroscopy, low-temperature N2 physisorption measurements, FTIR, FE-SEM, TEM, and XPS. The as-fabricated NiO/CMK-3 catalyst manifested a superior activity in the NaBH4-assisted reduction of methylene blue (MB) dye to its colorless leuco form. Remarkably, over 99% of 25 mg L-1 MB was reduced by 7.5 mM/L NaBH4 using 0.1 g L-1 NiO/CMK-3 within 3 min at room temperature. Furthermore, the kinetics study confirmed the appropriateness of the pseudo-first-order kinetic model for elucidating the kinetics of MB reduction by the catalyst. Importantly, the NiO/CMK-3 catalyst maintained almost constant catalytic activity even after 5 times of reuse in MB reduction, demonstrating its superior stability and reusable ability. So, NiO/CMK-5 appears as a promising heterogeneous catalyst for the effective remediation of dye-containing wastewater.

Supramolecular Interaction of Atenolol and Propranolol with ß-Cyclodextrin Spectroscopic Characterization and Analytical Application.

Atenolol (ATE) and propranolol (PRO) inclusion complexes with ß-cyclodextrin have been investigated in aqueous solution. The aqueous solution was examined and characterized using UV-vis, fluorescence spectroscopy, and 1H NMR. The physical mixture was characterized using FTIR. The existence of inclusion complexes is confirmed by observing changes in spectroscopic properties. The ATE complex with ß-CD exhibited an interaction as host and (ß-CD) as a guest in a 1:1 ratio, with an inclusion constant K of 2.09 × 10-3 µM-1, as determined by the typical double-reciprocal graphs. Similarly, the PRO complex with ß-CD exhibited an interaction as host and (ß-CD) guest in 1:1 and 1:2 stoichiometry at the same time; the inclusion constants were K1 = 5.80 × 10-5 µM-1 and K2 = 4.67 × 10-8 µM-1, as determined by typical double-reciprocal graphs. The variables influencing the formation of the inclusion complexes were investigated and optimized. Based on the enhancement in fluorescence intensity due to the formation of inclusion complexes, spectrofluorometric methods were developed and validated for determination of each drug's pharmaceutical formulation. The quantification of the fluorescence intensity for ATE and PRO was conducted at λex/λem 226/302 nm and λex/λem 231/338 nm, respectively. Under the optimal reaction circumstances, linear relationships with good correlation coefficients of 0.9918 and 0.99 were found in the concentration ranges of 0.3-1.7 µM, and 0.1-1.1 µM for ATE and PRO, respectively. The limits of detection (LODs) were found to be 0.13 and 0.01 µM for ATE and PRO, respectively. The suggested approach was effectively applied to the analysis of both drugs' pharmaceutical formulations.

Jaffe-Campanacci syndrome; a case series and review of the literature.

BACKGROUND: Jaffe-Campanacci syndrome is a rare syndrome, characterized by multiple non-ossifying fibromas (NOF) and cafe-au-lait patches. The name was coined in 1982 by Mirra after Jaffe who first described the case in 1958. Although it's suggested there is a relation with Neurofibromatosis type 1, there is still no consensus on whether Jaffe-Campanacci syndrome is a subtype or variant of neurofibromatosis-1(NF-1). CASE PRESENTATION: In this article, we present a case series of 2 patients. The first case is a 13-year-old male with Jaffe-Campanacci syndrome who presented with a distal femur fracture. His father had positive features of both Jaffe-Campanacci syndrome and NF-1, while his sister only had features of NF-1, so we presented both. CONCLUSION: Jaffe-Campanacci has a clear relationship with type 1 neurofibromatosis, which still has to be genetically established. Due to the presence of several large non-ossifying fibromas of the long bones, it is linked to a significant risk of pathological fractures. We concur with previous authors, that an osseous screening program should be performed for all patients with newly diagnosed type 1 neurofibromatosis, to identify non-ossifying fibromas and assess the potential for pathological fracture. Moreover, siblings of patients with NF-1 should be screened for multiple NOFs that may carry a high risk of pathological fractures.

Engineering nanomedicines for immunogenic eradication of cancer cells: Recent trends and synergistic approaches.

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment (TME) leading to failure of immune response. Numerous therapeutic strategies including chemotherapy, radiotherapy, photodynamic, photothermal, magnetic, chemodynamic, sonodynamic and oncolytic therapy, have been developed to induce immunogenic cell death (ICD) of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response. However, many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response. Here, we outline the current state of using nanomedicines for boosting ICD of cancer cells. Moreover, synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints, phagocytosis, macrophage polarization, tumor hypoxia, autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed. We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses. Endoplasmic reticulum localized ICD, focused ultrasound hyperthermia, cell membrane camouflaged nanomedicines, amplified reactive oxygen species (ROS) generation, metallo-immunotherapy, ion modulators and engineered bacteria are among the most innovative approaches. Various challenges, merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

Colistin-resistance genes in Escherichia coli isolated from patients with urinary tract infections.

BACKGROUND: The incidence of antimicrobial resistance is alarmingly high because it occurs in humans, environment, and animal sectors from a "One Health" viewpoint. The emergence of plasmid-carried mobile colistin-resistance (MCR) genes limits the efficacy of colistin, which is the last-line treatment for multidrug resistance (MDR) against gram-negative infections. OBJECTIVES: The current study aimed to investigate emergence of colistin-resistance (MCR 1-5) genes in E. coli isolated from patients with urinary tract infections (UTIs) in Jordan. METHODS: E. coli (n = 132) were collected from urine specimens. The E. coli isolated from human UTI patients were examined the resistance to colistin based on the presence of MCR (1-5). All isolates were tested against 20 antimicrobials using the standard disk diffusion method. The broth microdilution technique was used to analyze colistin resistance. In addition, the MCR (1-5) genes were detected using multiplex PCR. RESULTS: Out of the 132 isolates, 1 isolate was colistin-resistant, having a minimum inhibitory concentration of 8 µg/mL and possessing MCR-1. All the E. coli isolates showed high resistance to penicillin (100%), amoxicillin (79.55%), cephalexin (75.76%), nalidixic acid (62.88%), tetracycline (58.33%), or cefepime (53.79). CONCLUSION: To our knowledge, this is the first report on the presence of plasmid-coded MCR-1 in E. coli from a patient with UTIs in Jordan. This is a problematic finding because colistin is the last-line drug for the treatment of infections caused by MDR gram-negative bacteria. There is a crucial need to robustly utilize antibiotics to control and prevent the emergence and prevalence of colistin-resistance genes.

Polymer-Based Terbium Complex as a Fluorescent Probe for Cancer Antigen 125 Detection: A Promising Tool for Early Diagnosis of Ovarian Cancer.

A novel photoprobe, Tb-acetylacetone (Tb-ACAC) doped within a modified epoxy cellulose polymer immobilized with CA-125 monoclonal antibody, offers an accurate and highly selective method for early ovarian cancer (OC) diagnosis by detecting cancer antigen 125 (CA-125) in serum samples. This approach leverages quenching of the Tb-ACAC luminescence upon binding to CA-125. Characterization of the photoprobe film through UV-vis and fluorescence measurements confirmed the presence of Tb-ACAC within the polymer matrix. In aqueous solution (pH 6.8, λex = 365 nm), the characteristic emission band of Tb-ACAC at λem = 546.2 nm exhibited significant quenching upon CA-125 binding. This quenching effect enabled the sensitive and specific detection of CA-125 in diverse serum samples from OC patients, demonstrating the applicability, simplicity, and effectiveness of this novel approach.

Asymmetry in kinematics of dominant/nondominant lower limbs in central and lateral positioned college and sub-elite soccer players.

Change of direction, stops, and pivots are among the most common non-contact movements associated with anterior cruciate ligament (ACL) injuries in soccer. By observing these dynamic movements, clinicians recognize abnormal kinematic patterns that contribute to ACL tears such as increased knee valgus or reduced knee flexion. Different motions and physical demands are observed across playing positions, which may result in varied lower limb kinematic patterns. In the present study, 28 college and sub-elite soccer players performed four dynamic motions (change of direction with and without ball, header, and instep kick) with the goal of examining the effect of on-field positioning, leg dominance, and gender in lower body kinematics. Motion capture software monitored joint angles in the knee, hip, and ankle. A three-way ANOVA showed significant differences in each category. Remarkably, centrally positioned players displayed significantly greater knee adduction (5° difference, p = 0.013), hip flexion (9° difference, p = 0.034), hip adduction (7° difference, p = 0.016), and dorsiflexion (12° difference, p = 0.022) when performing the instep kick in comparison to their laterally positioned counterparts. These findings suggest that central players tend to exhibit a greater range of motion when performing an instep kicking task compared to laterally positioned players. At a competitive level, this discrepancy could potentially lead to differences in lower limb muscle development among on-field positions. Accordingly, it is suggested to implement position-specific prevention programs to address these asymmetries in lower limb kinematics, which can help mitigate dangerous kinematic patterns and consequently reduce the risk of ACL injury in soccer players.

Self-assembled monovalent lipidated mannose ligand as a standalone nanoadjuvant.

Subunit vaccines require an immunostimulant (adjuvant) and/or delivery system to induce immunity. However, currently, available adjuvants are either too dangerous in terms of side effects for human use (experimental adjuvants) or have limited efficacy and applicability. In this study, we examined the capacity of mannose-lipopeptide ligands to enhance the immunogenicity of a vaccine consisting of polyleucine(L15)-antigen conjugates anchored to liposomes. The clinically tested Group A Streptococcus (GAS) B-cell epitope, J8, combined with universal T helper PADRE (P) was used as the antigen. Six distinct mannose ligands were incorporated into neutral liposomes carrying L15PJ8. While induced antibody titers were relatively low, the ligand carrying mannose, glycine/lysine spacer, and two palmitic acids as liposomal membrane anchoring moieties (ligand 3), induced significantly higher IgG titers than non-mannosylated liposomes. The IgG titers were significantly enhanced when positively charged liposomes were employed. Importantly, the produced antibodies were able to kill GAS bacteria. Unexpectedly, the physical mixture of only ligand 3 and PJ8 produced self-assembled nanorods that induced antibody titers as high as those elicited by the lead liposomal formulation and antigen adjuvanted with the potent, but toxic, complete Freund's adjuvant (CFA). Antibodies produced upon immunization with PJ8 + 3 were even more opsonic than those induced by CFA + PJ8. Importantly, in contrast to CFA, ligand 3 did not induce observable adverse reactions or excessive inflammatory responses. Thus, we demonstrated that a mannose ligand, alone, can serve as an effective vaccine nanoadjuvant.

Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

Benzoate Derivatives Toxicity to Musca domestica Results in Severe Muscle Relaxation and Body Distortion.

The house fly, Musca domestica (Linnaeus) (Diptera: Muscidae), is a significant threat to human and animal health and is also resistant to a variety of insecticides. Plant-derived benzoates are known to have insecticidal activities against various insects. In this study, the larvicidal, pupicidal, and adulticidal activities of benzoate derivatives (benzyl alcohol BA, benzyl benzoate BB, and methyl benzoate MB) were assessed and investigated for their effects on larval structure and acetylcholinesterase activity. Six concentrations (2.5 to 100 mg/mL) of benzoate derivatives were applied to larvae and pupae through the residual film method and topical application, respectively. Meanwhile, concentrations from 0.625 to 50 mg/L air were applied to adult flies through a fumigation assay. BA and MB achieved promising results against larvae with LC50 values of 10.90 and 11.53 mg/mL, respectively. Moreover, BA killed 100% of the larvae at a concentration of 25 mg/mL, and MB achieved the same effect at a concentration of 50 mg/mL. Regarding the pupicidal activity, MB showed a percentage inhibition rate (PIR) of 100% at a concentration of 100 mg/mL, while the same effect was achieved by BA at a concentration of 50 mg/mL. Meanwhile, BB did not show any effect on the larvae or pupae at any of the tested concentrations. Moreover, the scanning microscopy observations on the treated larvae by BA and MB estimated flaccid and deformity in the larva body with a shrunken cuticle. Additionally, both BA and MB suppress nerve signal transmission by inhibiting acetylcholinesterase. In conclusion, the results of this study indicate that BA and MB may be useful in control housefly populations. These substances cause severe muscular relaxation and deformities in insects.

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis.

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 v/v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1ß, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

Studying the viability and growth kinetics of vancomycin-resistant Enterococcus faecalis V583 following femtosecond laser irradiation (420-465 nm).

Enterococcus faecalis is among the most resistant bacteria found in infected root canals. The demand for cutting-edge disinfection methods has rekindled research on photoinactivation with visible light. This study investigated the bactericidal activity of femtosecond laser irradiation against vancomycin-resistant Enterococcus faecalis V583 (VRE). The effect of parameters such as wavelength and energy density on the viability and growth kinetics of VRE was studied to design an optimized laser-based antimicrobial photoinactivation approach without any prior addition of exogenous photosensitizers. The most effective wavelengths were 430 nm and 435 nm at a fluence of 1000 J/cm2, causing a nearly 2-log reduction (98.6% and 98.3% inhibition, respectively) in viable bacterial counts. The colony-forming units and growth rate of the laser-treated cultures were progressively decreased as energy density or light dose increased at 445 nm but reached a limit at 1250 J/cm2. At a higher fluence of 2000 J/cm2, the efficacy was reduced due to a photobleaching phenomenon. Our results highlight the importance of optimizing laser exposure parameters, such as wavelength and fluence, in bacterial photoinactivation experiments. To our knowledge, this is the first study to report an optimized wavelength for the inactivation of VRE using visible femtosecond laser light.

Activation of peroxymonosulfate with ZIF-67-derived Co/N-doped porous carbon nanocubes for the degradation of Congo red dye.

In this study, porous carbon nanocubes encapsulated magnetic metallic Co nanoparticles (denoted as Co@N-PCNC) was prepared via pyrolyzing ZIF-67 nanocubes precursor at 600 °C and characterized by various technologies. It was used to activate peroxymonosulfate (PMS) to degrade Congo red (CR) dye efficiently. Over 98.45% of 50 mg L-1 CR was degraded using 0.033 mM PMS activated by 75 mg L-1 Co@N-PCNC within 12 min. The free radical quenching experiments were performed to reveal the nature of the reactive oxygen species radicals generated throughout the catalytic oxidation of CR. The effects of common inorganic anions and the water matrix on CR removal were studied. Moreover, the results of the kinetic study revealed the suitability of the pseudo-first-order and Langmuir-Hinshelwood kinetic models for illustrating CR degradation using the Co@N-PCNC/PMS system. Ultimately, the Co@N-PCNC displayed good operational stability, and after five cycles, the CR removal rate can still maintain over 90% after 12 min.