Microfluidic Platform for Generating and Releasing Patient-Derived Cancer Organoids with Diverse Shapes: Insight into Shape-Dependent Tumor Growth.

Multicellular spheroids and patient-derived organoids find many applications in fundamental research, drug discovery, and regenerative medicine. Advances in the understanding and recapitulation of organ functionality and disease development require the generation of complex organoid models, including organoids with diverse morphologies. Microfluidics-based cell culture platforms enable time-efficient confined organoid generation. However, the ability to form organoids with different shapes with a subsequent transfer from microfluidic devices to unconstrained environments for studies of morphology-dependent organoid growth is yet to be demonstrated. Here, a microfluidic platform is introduced that enables high-fidelity formation and addressable release of breast cancer organoids with diverse shapes. Using this platform, the impact of organoid morphology on their growth in unconstrained biomimetic hydrogel is explored. It is shown that proliferative cancer cells tend to localize in high positive curvature organoid regions, causing their faster growth, while the overall growth pattern of organoids with diverse shapes tends to reduce interfacial tension at the organoid-hydrogel interface. In addition to the formation of organoids with diverse morphologies, this platform can be integrated into multi-tissue micro-physiological systems.

Dihydroxyphenylalanine-conjugated high molecular weight polyethylenimine for targeted delivery of Plasmid.

High molecular weight polyethylenimine (HMW PEI; branched 25 kDa PEI) has been widely investigated for gene delivery due to its high transfection efficiency. However, the toxicity and lack of targeting to specific cells have limited its clinical application. In the present investigation, L-3, 4-dihydroxyphenylalanine (L-DOPA) was conjugated on HMW PEI in order to target L-type amino acid transporter 1 (LAT-1) and modulate positive charge density on the surface of polymer/plasmid complexes (polyplexes). The results of biophysical characterization revealed that the PEI conjugates are able to form nanoparticles ≤ 180 nm with the zeta potential ranging from + 9.5-12.4 mV. These polyplexes could condense plasmid DNA and protect it against nuclease digestion at the carrier to plasmid ratios higher than 4. L-DOPA conjugated PEI derivatives were complexed with a plasmid encoding human interleukin-12 (hIL-12). Targeted polyplexes showed up to 2.5 fold higher transfection efficiency in 4T1 murine mammary cancer cell line, which expresses LAT-1, than 25 kDa PEI polyplexes prepared in the same manner. The cytotoxicity of these polyplexes was also substantially lower than the unmodified parent HMW PEI. These results support the use of L-3, 4-dihydroxyphenylalanine derivatives of PEI in any attempt to develop a LAT-1 targeted gene carrier.

In Silico Design of CT26 Polytope and its Surface Display by ClearColi™-Derived Outer Membrane Vesicles as a Cancer Vaccine Candidate Against Colon Carcinoma.

Simultaneous targeting of several mutations can be useful in colorectal cancer (CRC) due to its heterogeneity and presence of somatic mutations. As CT26 mutations and expression profiles resemble those of human CRC, we focused on designing a polyepitope vaccine based on CT26 neoepitopes. Due to its low immunogenicity, outer membrane vesicles (rOMV) as an antigen delivery system and adjuvant was applied. Herein, based on previous experimental and our in silico studies four CT26 neoepitopes with the ability to bind MHC-I and MHC-II, TCR, and induce IFN-α production were selected. To increase their immunogenicity, the gp70 and PADRE epitopes were added. The order of the neoepitopes was determined through 3D structure analysis using ProSA, Verify 3D, ERRAT, and Ramachandran servers. The stable peptide-protein docking between the selected epitopes and MHC alleles strengthen our prediction. The CT26 polytope vaccine sequence was fused to the C-terminal of cytolysin A (ClyA) anchor protein and rOMVs were isolated from endotoxin-free ClearColi™ strain. The results of the C-ImmSim server showed that the ClyA-CT26 polytope vaccine could induce T and B cells immunity.The ClyA-CT26 polytope was characterized as a soluble, stable, immunogen, and non-allergen vaccine and optimized for expression in ClearColi™ 24 h after induction with 1 mM IPTG at 25 °C. Western blot analysis confirmed the expression of ClyA-CT26 polytope by ClearColi™ and also on ClearColi™-derived rOMVs. In conclusion, we found that ClearColi™-derived rOMVs with CT26 polytope can deliver CRC neoantigens and induce antitumor immunity, but in vivo immunological studies are needed to confirm vaccine efficacy.

Experiences and attitudes of clinical and academic nurses about infection prevention and control nursing curriculum and duties - a qualitative study.

BACKGROUND: Infectious diseases are becoming more widespread and re-emerging, causing psychological, social, economic, and health effects at both national and international levels. Specialist nurses can help prevent and control these infections. However, in Iran, there are currently no specialist infection prevention and control (IPC) nurses to manage and control infections. This study aims to explore clinical and academic nurses' attitudes toward IPC nursing curriculum and duties. METHODS: The study used a qualitative content analysis approach. Thirty-six participants, including clinical and academic nurses, were selected using a purposeful sampling method. Data was collected through seven focused group discussions. The accuracy and validity of the research tools were measured using the Four-Dimension Criteria developed by Lincoln and Guba. Data analysis was conducted using directed content analysis. RESULTS: The data analysis of the discussions held in the seven focus groups extracted 628 codes. Three themes were developed from the qualitative analysis: "Core characteristics of the curriculum", "Expected competencies and skills", and "Evaluation." These themes were derived from nine main categories and 25 subcategories. CONCLUSIONS: Specialist IPC nurses can play important roles in various positions and environments. Therefore, educational policymakers in Iran should consider establishing IPC nursing courses. It is also recommended that policymakers and decision-makers in the nursing field of other less developed countries should prioritize this issue.

Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.

IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Predisposing factors of using cosmetics in Iranian female students: application of prototype willingness model.

Background and aim: The use of cosmetics among Iranian teenagers and youths has increased more than ever before. This study investigated the predisposing factors of cosmetic use in female students of Ardabil University of Medical Sciences by using the prototype willingness model (PWM). Methods: This cross-sectional study was conducted with 384 students, selected based on multistage sampling. Data were collected using a two-part questionnaire that included demographic variables and PWM questions. Then multiple regression analysis was used in SPSS (version 20). Results: There was a significant difference in the frequency of daily cosmetic use based on the education levels (F = 3.845, p-value = 0.034). The average daily use of cosmetics was higher in students whose use of cosmetics was high in their family (p = 0.024) and friends (p-value = 0.023). Prototypes were the strongest predictor of using cosmetics (OR = 1.317, p-value <0.001), followed by attitude (OR = 1.241, p-value <0.001). Conclusion: Prototypes (social imagination) and attitudes were the main predictors of using cosmetics among female students. To be effective in targeting cosmetic use, interventions must target both social and individual paths.

Living in urban or rural environments affect the sleep quality of the elderly in Bushehr (Southern Iran): emphasizing the active and inactive of the elderly.

INTRODUCTION: Sleep disorders have a significant negative impact on mental and physical health, especially among the elderly. Various factors can affect the sleep quality of elderly people. The aim of this research to investigate the effect of urban and rural environments on the sleep quality of elderly people with emphasis on physical activity. METHOD: Four hundred and thirty-nine elderly people (226 city residents and 213 village residents) in urban and rural areas of Bushehr (Southern Iran), volunteered to participate in the present study. Information was collected via the General information questionnaire and Petersburg Sleep Questionnaire. RESULT: The results showed that active elderly women (p < 0.001), and total active elderly (male + female) (p < 0.001) living in urban areas compared to inactive elderly and also in rural areas active elderly women (p < 0.001), active elderly men (p < 0.001) and total active elderly (male + female) (p < 0.001) had better overall sleep quality in compared to inactive elderly. Also, elderly men (p < 0.001) and the total elderly (male + female) (p < 0.001) living in urban areas had better sleep quality than the elderly in rural areas. CONCLUSION: Based on the findings, it can be concluded that the way of life (being active) as well as the living environment can affect the sleep quality of elderly people, so that active elderly people and also elderly people living in urban environments had better sleep quality.

Preparation and characterization of artemether-loaded niosomes in Leishmania major-induced cutaneous leishmaniasis.

Cutaneous leishmaniasis is the most prevalent form of leishmaniasis worldwide. Although various anti-leishmanial regimens have been considered, due to the lack of efficacy or occurrence of adverse reactions, design and development of novel topical delivery systems would be essential. This study aimed to prepare artemether (ART)-loaded niosomes and evaluate their anti-leishmanial effects against Leishmania major. ART-loaded niosomes were prepared through the thin-film hydration technique and characterized in terms of particle size, zeta potential, morphology, differential scanning calorimetry, drug loading, and drug release. Furthermore, anti-leishmanial effect of the preparation was assessed in vitro and in vivo. The prepared ART-loaded niosomes were spherical with an average diameter of about 100 and 300 nm with high encapsulation efficiencies of > 99%. The results of in vitro cytotoxicity revealed that ART-loaded niosomes had significantly higher anti-leishmanial activity, lower general toxicity, and higher selectivity index (SI). Half-maximal inhibitory concentration (IC50) values of ART, ART-loaded niosomes, and liposomal amphotericin B were 39.09, 15.12, and 20 µg/mL, respectively. Also, according to the in vivo study results, ART-loaded niosomes with an average size of 300 nm showed the highest anti-leishmanial effects in animal studies. ART-loaded niosomes would be promising topical drug delivery system for the management of cutaneous leishmaniasis.

Echinacea: Bioactive Compounds and Agronomy.

For centuries, medicinal plants have been used as sources of remedies and treatments for various disorders and diseases. Recently, there has been renewed interest in these plants due to their potential pharmaceutical properties, offering natural alternatives to synthetic drugs. Echinacea, among the world's most important medicinal plants, possesses immunological, antibacterial, antifungal, and antiviral properties. Nevertheless, there is a notable lack of thorough information regarding the echinacea species, underscoring the vital need for a comprehensive review paper to consolidate existing knowledge. The current review provides a thorough analysis of the existing knowledge on recent advances in understanding the physiology, secondary metabolites, agronomy, and ecology of echinacea plants, focusing on E. purpurea, E. angustifolia, and E. pallida. Pharmacologically advantageous effects of echinacea species on human health, particularly distinguished for its ability to safeguard the nervous system and combat cancer, are discussed. We also highlight challenges in echinacea research and provide insights into diverse approaches to boost the biosynthesis of secondary metabolites of interest in echinacea plants and optimize their large-scale farming. Various academic databases were employed to carry out an extensive literature review of publications from 2001 to 2024. The medicinal properties of echinacea plants are attributed to diverse classes of compounds, including caffeic acid derivatives (CADs), chicoric acid, echinacoside, chlorogenic acid, cynarine, phenolic and flavonoid compounds, polysaccharides, and alkylamides. Numerous critical issues have emerged, including the identification of active metabolites with limited bioavailability, the elucidation of specific molecular signaling pathways or targets linked to echinacoside effects, and the scarcity of robust clinical trials. This raises the overarching question of whether scientific inquiry can effectively contribute to harnessing the potential of natural compounds. A systematic review and analysis are essential to furnish insights and lay the groundwork for future research endeavors focused on the echinacea natural products.

Evaluating an extraction-free sample preparation method for multiplex detection of SARS-Cov-2, influenza A/B, and RSV with implementation on a microfluidic chip.

Following the relaxation of COVID-19 restrictions, other respiratory viruses such as influenza and respiratory syncytial virus (RSV), whose transmission were decreased due to COVID-19 precautions, are rising again. Because of similar clinical features and reported co-infections, multiplex detection of SARS-CoV-2, influenza A/B, and RSV is required to use specific treatments. This study assessed an extraction-free sample preparation (heat treatment at 95°C for 3 minutes) for multiplex detection using rRT-PCR. Despite an observed Ct-delay (∆Ct) averageing 1.26 compared to the standard method, an acceptable total sensitivity of 92 % and a negative predictive value (NPV) of 96 % were obtained. Moreover, Implementation on a microfluidic chip demonstrated efficiency, maintaining an excellent correlation (R2=0.983) with the standard method. Combining this extraction-free procedure with rRT-PCR on a microfluidic chip seems promising, because it simplifies the design and reduces the cost and complexity of the integrated assay for multiplex detection of SARS-CoV-2, influenza A/B, and RSV.

microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/ß-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

Investigation the biological activities and the metabolite profiles of endophytic fungi isolated from Gundelia tournefortii L.

Endophytic fungi are microorganisms that are considered as a potential source of natural compounds, and can be applied in various industries. The aims of this research were molecular identification of endophytic fungi isolated from the Gundelia tournefortii stems, and investigation their biological activities as well as phenolic and fatty acid profile. Surface sterilized stems of G. tournefortii were placed on potato dextrose agar (PDA) to isolate the fungal endophytes. Genomic DNA was extracted by CTAB method, and PCR amplification was performed by ITS 1 and ITS 4 as primers. The enzyme production of endophytic fungi was determined based on the formation of a clear zone that appeared around the colonies of fungus. The anti-oxidant activity was evaluated by measuring the amount of free radicals DPPH. Also, the total phenol and flavonoid contents were measured obtained by Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Moreover, the separation and identification of phenolic acids and fatty acids were done by HPLC and GC, respectively. Phylogenetic analysis was done based on the Internal Transcribed Spacer (ITS) region, and five isolates were identified as following: Aspergillus niger, Penicillium glabrum, Alternaria alternata, A. tenuissima, and Mucor circinelloides. Evaluation of the enzymatic properties showed that P. gabrum (31 ± 1.9 mm), and A. niger (23 ± 1.7) had more ability for producing pectinase and cellulase. The anti-oxidant activity of isolates showed that A. alternata extract (IC50 = 471 ± 29 µg/mL) had the highest anti-oxidant properties, followed by A. tenuissima extract (IC50 = 512 ± 19 µg/mL). Also, the extract of A. alternata had the greatest amount of total phenols and flavonoids contents (8.2 ± 0.4 mg GAL/g and 2.3 ± 0.3 mg QE/g, respectively). The quantification analysis of phenolic acid showed that rosmarinic acid, para-coumaric acid, and meta-coumaric acid (42.02 ± 1.31, 7.53 ± 0.19, 5.41 ± 0.21 mg/g, respectively) were the main phenolic acids in the studied fungi. The analysis of fatty acids confirmed that, in all fungi, the main fatty acids were stearic acid (27.9-35.2%), oleic acid (11.3-17.3%), palmitic acid (16.9-23.2%), linoleic acid (5.8-11.6%), and caprylic acid (6.3-10.9%). Our finding showed that endophytic fungi are a source of bioactive compounds, which could be used in various industries. This is the first report of endophytic fungi associated with G. tournefortii, which provides knowledge on their future use on biotechnological processes.

An Automated Single-Cell Droplet-Digital Microfluidic Platform for Monoclonal Antibody Discovery.

Monoclonal antibody (mAb) discovery plays a prominent role in diagnostic and therapeutic applications. Droplet microfluidics has become a standard technology for high-throughput screening of antibody-producing cells due to high droplet single-cell confinement frequency and rapid analysis and sorting of the cells of interest with their secreted mAbs. In this work, a new method is described for on-demand co-encapsulation of cells that eliminates the difficulties associated with washing in between consecutive steps inside the droplets and enables the washing and addition of fresh media. The new platform identifies hybridoma cells that are expressing antibodies of interest using antibody-characterization assays to find the best-performing or rare-cell antibody candidates.

A versatile theranostic magnetic polydopamine iron oxide NIR laser-responsive nanosystem containing doxorubicin for chemo-photothermal therapy of melanoma.

Theranostics nanoparticles (NPs) have recently received much attention in cancer imaging and treatment. This study aimed to develop a multifunctional nanosystem for the targeted delivery of photothermal and chemotherapy agents. Fe3O4 NPs were modified with polydopamine, bovine serum albumin, and loaded with DOX via a thermal-cleavable Azo linker (Fe3O4@PDA@BSA-DOX). The size of Fe3O4@PDA@BSA NPs was approximately 98 nm under the desired conditions. Because of the ability of Fe3O4 and PDA to convert light into heat, the temperature of Fe3O4@PDA@BSA NPs increased to approximately 47 °C within 10 min when exposed to an 808 nm NIR laser with a power density of 1.5 W/cm2. The heat generated by the NIR laser leads to the breaking of AZO linker and drug release. In vivo and in vitro results demonstrated that prepared NPs under laser irradiation successfully eradicated tumor cells without any significant toxicity effect. Moreover, the Fe3O4@PDA@BSA NPs exhibited the potential to function as a contrasting agent. These NPs could accumulate in tumors with the help of an external magnet, resulting in a significant enhancement in the quality of magnetic resonance imaging (MRI). The prepared novel multifunctional NPs seem to be an efficient system for imaging and combination therapy in melanoma.

Recent findings in methanotrophs: genetics, molecular ecology, and biopotential.

The potential consequences for mankind could be disastrous due to global warming, which arises from an increase in the average temperature on Earth. The elevation in temperature primarily stems from the escalation in the concentration of greenhouse gases (GHG) such as CO2, CH4, and N2O within the atmosphere. Among these gases, methane (CH4) is particularly significant in driving alterations to the worldwide climate. Methanotrophic bacteria possess the distinctive ability to employ methane as both as source of carbon and energy. These bacteria show great potential as exceptional biocatalysts in advancing C1 bioconversion technology. The present review describes recent findings in methanotrophs including aerobic and anaerobic methanotroph bacteria, phenotypic characteristics, biotechnological potential, their physiology, ecology, and native multi-carbon utilizing pathways, and their molecular biology. The existing understanding of methanogenesis and methanotrophy in soil, as well as anaerobic methane oxidation and methanotrophy in temperate and extreme environments, is also covered in this discussion. New types of methanogens and communities of methanotrophic bacteria have been identified from various ecosystems and thoroughly examined for a range of biotechnological uses. Grasping the processes of methanogenesis and methanotrophy holds significant importance in the development of innovative agricultural techniques and industrial procedures that contribute to a more favorable equilibrium of GHG. This current review centers on the diversity of emerging methanogen and methanotroph species and their effects on the environment. By amalgamating advanced genetic analysis with ecological insights, this study pioneers a holistic approach to unraveling the biopotential of methanotrophs, offering unprecedented avenues for biotechnological applications. KEY POINTS: • The physiology of methanotrophic bacteria is fundamentally determined. • Native multi-carbon utilizing pathways in methanotrophic bacteria are summarized. • The genes responsible for encoding methane monooxygenase are discussed.

Development of kojic acid loaded collagen-chitosan nanoparticle as skin lightener product: in vitro and in vivo assessment.

In the present study, an ionic gelation and ultrasonic approach was performed to produce kojic acid (KA) loaded chitosan(CS)/collagen(CN) nanoparticle(NP) (CSCN-NP) which aimed to increase the dermal delivery and anti-pigmentation effect. To optimize the CSCN-NP the effect of the amount of CN was investigated. The results showed that increasing CN from 0 to 500 mg increased the mean particle size and entrapment efficiency of KA-CSCN-NP from 266.07 ± 9.30 nm to 404.23 ± 9.44 nm and 17.37 ± 2.06% to 82.34 ± 2.16%, respectively. Differential scanning calorimetry confirmed the amorphous form of KA in CSCN-NP, while scanning electron microscopy revealed that the nanoparticles were spherical. There was no chemical interaction between KA and the other components base on attenuated total reflectance-Fourier transform infrared spectroscopy. The skin permeability test showed that KA-CSCN-NP gel delivered more KA to the dermal layers (29.16 ± 1.67% or 537.26 ± 537.26 µg/cm2) and receiver compartment (15.04 ± 1.47% or 277.15 ± 27.22 µg/cm2) compared to KA plain gel. In vitro cytotoxicity assay demonstrated that the improved KA-CSCN-NP was non-toxic. Dermal irritating test on Wistar rats showed that the KA gel was non-irritating. Furthermore, KA-CSCN-NP was found to inhibit melanin formation to a greater extent than free KA and significantly inhibited L-dopa auto-oxidation (94.80 ± 2.41%) compared to pure kojic acid solution (75.28 ± 3.22%). The observations of this study revealed that the produced KA-CSCN-NP might be used as a potential nano-vehicle for KA dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.

Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.

Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease.

Importance: Low-dose methotrexate is used to treat rheumatoid arthritis and psoriasis. Due to its kidney elimination, better evidence is needed to inform its safety in adults with chronic kidney disease (CKD). Objectives: To compare the 90-day risk of serious adverse events among adults with CKD who started low-dose methotrexate vs those who started hydroxychloroquine and to compare the risk of serious adverse events among adults with CKD starting 2 distinct doses of methotrexate vs those starting hydroxychloroquine. Design, Setting, and Participants: This retrospective, population-based, new-user cohort study was conducted in Ontario, Canada (2008-2021) using linked administrative health care data. Adults aged 66 years or older with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis) who started low-dose methotrexate (n = 2309) were matched 1:1 with those who started hydroxychloroquine. Exposure: Low-dose methotrexate (5-35 mg/wk) vs hydroxychloroquine (200-400 mg/d). Main Outcome and Measure: The primary outcome was a composite of serious adverse events: a hospital visit with myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of starting the study drug. Prespecified subgroup analyses were conducted by eGFR category. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RRs) were obtained using modified Poisson regression, and risk differences (RDs) using binomial regression. Results: In a propensity score-matched cohort of 4618 adults with CKD (3192 [69%] women; median [IQR] age, 76 [71-82] years), the primary outcome was higher in patients who started low-dose methotrexate vs those who started hydroxychloroquine (82 of 2309 [3.55%] vs 40 of 2309 [1.73%]; RR, 2.05 (95% CI, 1.42-2.96); RD, 1.82% [95% CI, 0.91%-2.73%]). In subgroup analysis, the risks increased progressively at lower eGFR (eg, eGFR <45 mL/min/1.73 m2: RR, 2.79 [95% CI, 1.51-5.13]). In the secondary comparison with hydroxychloroquine, methotrexate users at 15 to 35 mg/wk had a higher risk of the primary outcome. Conclusions and Relevance: In this cohort of 4618 older patients with CKD, the 90-day risk of serious adverse events was higher among those who started low-dose methotrexate than those who started hydroxychloroquine. If verified, these risks should be balanced against the benefits of low-dose methotrexate use.

Recent advances in various bio-applications of bacteria-derived outer membrane vesicles.

Outer membrane vesicles (OMVs) are spherical nanoparticles released from gram-negative bacteria. OMVs were originally classified into native 'nOMVs' (produced naturally from budding of bacteria) and non-native (produced by mechanical means). nOMVs and detergent (dOMVs) are isolated from cell supernatant without any detergent cell disruption techniques and through detergent extraction, respectively. Growth stages and conditions e.g. different stress factors, including temperature, nutrition deficiency, and exposure to hazardous chemical agents can affect the yield of OMVs production and OMVs content. Because of the presence of bacterial antigens, pathogen-associated molecular patterns (PAMPs), various proteins and the vesicle structure, OMVs have been developed in many biomedical applications. OMVs due to their size can be phagocytized by APCs, enter lymph vessels, transport antigens efficiently, and induce both T and B cells immune responses. Non-engineered OMVs have been frequently used as vaccines against different bacterial and viral infections, and various cancers. OMVs can also be used in combination with different antigens as an attractive vaccine adjuvant. Indeed, foreign antigens from target microorganisms can be trapped in the lumen of nonpathogenic vesicles or can be displayed on the surface through bacterial membrane protein to increase the immunogenicity of the antigens. In this review, different factors affecting OMV production including time of cultivation, growth media, stress conditions and genetic manipulations to enhance vesiculation will be described. Furthermore, recent advances in various biological applications of OMVs such as vaccine, drug delivery, cancer therapy, and enzyme carrier are discussed. Generally, the application of OMVs as vaccine carrier in three categories (i.e., non-engineered OMVs, OMVs as an adjuvant, recombinant OMVs (rOMVs)), as delivery system for small interfering RNA and therapeutic agents, and as enzymes carrier will be discussed.