Reduced Side Effects Research Articles

In-depth in silico and in vitro screening of selected edible plants for identification of selective C-domain ACE-1 inhibitor and its synergistic effect with captopril

Angiotensin converting enzyme (ACE) is a crucial enzyme in renin angiotensin aldosterone system (RAAS), having a pivotal role in blood pressure regulation. Despite its widespread medical applications in hypertension, heart diseases, diabetic nephropathy, and many others, inhibitors of the ACE enzyme suffer from different side effects that limit their use. Plants and natural products are the primary sources of renewable natural compounds that could act as potential leads for different ailments. The following study represents the identification of ACE inhibitors from carefully selected edible plants through adopting combined in silico techniques with biological testing. Molecular docking studies were performed on 1526 phytoconstituents present in 19 edible plants. Biochemical testing of extracts from the top ten hit plants revealed that Moringa oleifera is a potent ACE-1 inhibitor with an IC50 value of 104.4 μg/mL. On top of that, its isolated compound 4-O-caffeoylquinic acid had IC50 value of 62.92 μM. In silico combination analysis showed synergistic effects of moringa extract and 4-O-caffeoylquinic acid combined with captopril, especially at 90% effect level. This, in turn, is likely to reduce side effects and toxicity. Furthermore, selective domain docking showed strong affinity of 4-O-caffeoylquinic acid to the C-domain of ACE enzyme. Since the inflammatory responses and elevated reactive oxygen species in vasculature increase hypertension, the antioxidant effect of the compound was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and it possessed an acceptable effect with IC50 value of 73.82 μM. These findings advocate the antihypertensive potential of moringa leaves extract. Besides, we introduce 4-O-caffeoylquinic acid as a candidate lead for the design of safe, bidirectional ACE-1 inhibitor with strong antioxidant effect.

Precision Medicine for COVID-19 Based on the Inflammatory Response

Background The threat due to the global pandemic of the coronavirus disease 2019 (COVID-19) demands a search for effective treatments to combat the severity of the infections and their associated morbidity and mortality in vulnerable populations. One of the medications with putative antiviral, anti-inflammatory, and immunomodulatory effects is fluvoxamine, a selective serotonin reuptake inhibitor and σ-1 receptor agonist. A few studies have reported doses of 100–300 mg/day to be effective. Aim This retrospective study evaluates the outcomes of an individually tailored dosing strategy for fluvoxamine, based on measurements of inflammatory status, in treating COVID-19-positive individuals in India. Methods This study included patients with severe acute respiratory syndrome coronavirus 2 infection visiting the outpatient department of a super speciality hospital in India from February to July 2021. Fluvoxamine was initiated at 50 mg or 100 mg twice daily based on their individual C-reactive protein (CRP) and D-dimer status. By day five, patients with rising or static levels of CRP and D-dimer were up-titrated. Results In a population of 104 individuals infected with COVID-19, 10 required up-titration of dose, and 94 patients did not need up-titration. Overall, there was very low mortality (N = 1) and hospitalization rate (8.7%). Those individuals who required an up-titration on day five had significantly elevated CRP and D-dimer levels compared to those who were maintained at the initial dose of 50 mg twice daily. In such patients, up-titration of the dose on day 5 appeared to offer better treatment benefits and outcomes. In our study population, there was only one mortality during the course of COVID-19. Conclusions Given the individual variability in the host immune response to severe acute respiratory syndrome coronavirus 2 infection, tailoring the dose of a drug such as fluvoxamine based on the inflammatory status of the individual may be beneficial. Individually tailored dosing could combat disease progression while reducing side effects.

Neuroprotective effects of chlorogenic acid against oxidative stress in rats subjected to lithium-pilocarpine-induced status epilepticus.

Epilepsy is a condition marked by sudden, self-sustained, and recurring brain events, showcasing unique electro-clinical and neuropathological phenomena that can alter the structure and functioning of the brain, resulting in diverse manifestations. Antiepileptic drugs (AEDs) can be very effective in 30% of patients in controlling seizures. Several factors contribute to this: drug resistance, individual variability, side effects, complexity of epilepsy, incomplete understanding, comorbidities, drug interactions, and no adherence to treatment. Therefore, research into new AEDs is important for several reasons such as improved efficacy, reduced side effects, expanded treatment options, treatment for drug-resistant epilepsy, improved safety profiles, targeted therapies, and innovation and progress. Animal models serve as crucial biological tools for comprehending neuronal damage and aiding in the discovery of more effective new AEDs. The utilization of antioxidant agents that act on the central nervous system may serve as a supplementary approach in the secondary prevention of epilepsy, both in laboratory animals and potentially in humans. Chlorogenic acid (CGA) is a significant compound, widely prevalent in numerous medicinal and food plants, exhibiting an extensive spectrum of biological activities such as neuroprotection, antioxidant, anti-inflammatory, and analgesic effects, among others. In this research, we assessed the neuroprotective effects of commercially available CGA in Wistar rats submitted to lithium-pilocarpine-induced status epilepticus (SE) model. After 72-h induction of SE, rats received thiopental and were treated for three consecutive days (1st, 2nd, and 3rd doses). Next, brains were collected and studied histologically for viable cells in the hippocampus with staining for cresyl-violet (Nissl staining) and for degenerating cells with Fluoro-Jade C (FJC) staining. Moreover, to evaluate oxidative stress, the presence of malondialdehyde (MDA) and superoxide dismutase (SOD) was quantified. Rats administered with CGA (30 mg/kg) demonstrated a significant decrease of 59% in the number of hippocampal cell loss in the CA3, and of 48% in the hilus layers after SE. A significant reduction of 75% in the cell loss in the CA3, shown by FJC+ staining, was also observed with the administration of CGA (30 mg/kg). Furthermore, significant decreases of 49% in MDA production and 72% in the activity of SOD were seen, when compared to animals subjected to SE that received vehicle. This study introduces a novel finding: the administration of CGA at a dosage of 30 mg/kg effectively reduced oxidative stress induced by lithium-pilocarpine, with its effects lasting until the peak of neural damage 72 h following the onset of SE. Overall, the research and development of new AEDs are essential for advancing epilepsy treatment, improving patient outcomes, and ultimately enhancing the quality of life for individuals living with epilepsy.

Impact of depressive symptoms on adverse effects in people with epilepsy on antiseizure medication therapy.

We studied the impact of depressive symptoms on adverse effects (AEs) in people with epilepsy (PWE) on antiseizure medication (ASM) therapy. An effect of depression on the AE burden has already been reported. We studied the correlation of various depressive symptoms with specific AEs to assess which AEs are especially prone to being confounded by particular depressive symptoms. PWE filled in a variety of questionnaires including the "Neurological Disorder Depression Inventory for Epilepsy" (NDDI-E), "Emotional Thermometers 4" (ET4) and "Liverpool Adverse Events Profile" (LAEP). Depression was defined by a NDDI-E score > 13. Depressive symptoms consisted of NDDI-E and ET4 items. Discriminant analysis identified those AEs (=LAEP items) that were most highly influenced by depression. Logistic regression analysis yielded correlations of different depressive symptoms with specific AEs. We included 432 PWE. The strongest discriminators for depression were the LAEP items "Depression", "Nervousness/agitation," and "Tiredness". Out of all depressive symptoms "Everything I do is a struggle" most strongly correlated with total LAEP score (odds ratio [OR] = 3.1) and correlated with all but one LAEP item. Other depressive symptoms correlated to varying degrees with total LAEP and item scores. The number of ASMs, lack of seizure remission, and female gender correlated with high LAEP scores. To the best of our knowledge, we are the first to show that various depressive symptoms correlate with specific LAEP items. This information can be helpful for quick evaluation of whether the reporting of different LAEP items may be confounded by particular depressive symptoms. This is relevant because changes in therapy may differ depending on if AEs are confounded by depressive symptoms. Simply reporting a particular depressive symptom may give a clue to whether specific AEs are confounded by depression. Our findings confirm the importance of screening for depression in all PWE. In this study we measured depressive disorder and side effects caused by medication used to treat epilepsy with self-reported questionnaires in a cohort of people with epilepsy. We found depressive disorder to influence the perception of side effects that are caused by drugs used to treat epilepsy. This knowledge can help to identify if the reporting of side effects is influenced by depression. Treating depression may help to reduce side effects and may thus increase the tolerability of anti-epileptic medication. People who tolerate their medication are more likely to take it and are thus less likely to develop epileptic seizure.

ECM1 and KRT6A are involved in tumor progression and chemoresistance in the effect of dexamethasone on pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Neoadjuvant chemotherapy is an effective PDAC treatment option, but chemotherapy causes unfavorable side effects. Glucocorticoids (e.g., dexamethasone [DEX]) are administered to reduce side effects of chemotherapy for solid tumors, including pancreatic cancer. Glucocorticoids have both beneficial and detrimental effects, however. We investigated the functional changes and gene-expression profile alterations induced by DEX in PDAC cells. PDAC cells were treated with DEX, and the cell proliferation, migration, invasion, and chemosensitivity to gemcitabine (GEM) were evaluated. The results demonstrated decreased cell proliferative capacity, increased cell migration and invasion, and decreased sensitivity to GEM. A comprehensive genetic analysis revealed marked increases in ECM1 and KRT6A in DEX-treated PDAC cells. We evaluated the effects of ECM1 and KRT6A expression by using PDAC cells transfected with those genes. Neither ECM1 nor KRT6A changed the cells' proliferation, but each enhanced cell migration and invasion. ECM1 decreased sensitivity to GEM. We also assessed the clinicopathological significance of the expressions of ECM1 and KRT6A in 130 cases of PDAC. An immunohistochemical analysis showed that KRT6A expression dominated the poorly differentiated areas. High expressions of these two proteins in PDAC were associated with a poorer prognosis. Our results thus demonstrated that DEX treatment changed PDAC cells' functions, resulting in decreased cell proliferation, increased cell migration and invasion, and decreased sensitivity to GEM. The molecular mechanisms of these changes involve ECM1 and KRT6A, whose expressions are induced by DEX.

Anticancer Activity of Rice Callus Suspension Cultures from Aromatic Varieties and Metabolites Regulated in Treated Cancer Cell Lines

Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures (RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.

Recent Advances in Nanotechnology for the Treatment of Dry Eye Disease.

Dry eye disease (DED) incidence is continuously growing, positioning it to become an emergent health issue over the next few years. Several topical treatments are commonly used to treat DED; however, reports indicate that only a minor proportion of drug bioavailability is achieved by the majority of eye drops available on the market. In this context, enhancing drug ability to overcome ocular barriers and prolonging its residence time on the ocular surface represent a new challenge in the field of ocular carrier systems. Therefore, research has focused on the development of multi-functional nanosystems, such as nanoemulsions, liposomes, dendrimers, hydrogels, and other nanosized carriers. These systems are designed to improve topical drug bioavailability and efficacy and, at the same time, require fewer daily administrations, with potentially reduced side effects. This review summarizes the different nanotechnologies developed, their role in DED, and the nanotechnology-based eyedrops currently approved for DED treatment.

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, migration and drug resistance. To address the roles of BRD4 in cancer, several drugs that specifically target BRD4 have been developed. Inhibition of BRD4 has shown promising results in preclinical models, with several BRD4 inhibitors undergoing clinical trials for the treatment of various cancers. Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of cancers, remains a health challenge with a high incidence rate and poor prognosis. Conventional therapies for HNSCC often cause adverse effects to the patients. Targeting BRD4, therefore, represents a promising strategy to sensitize HNSCC to chemo‑ and radiotherapy allowing de‑intensification of the current therapeutic regime and subsequent reduced side effects. However, further studies are required to fully understand the underlying mechanisms of action of BRD4 in HNSCC in order to determine the optimal dosing and administration of BRD4‑targeted drugs for the treatment of patients with HNSCC.

Coadministration of doxorubicin with vitamin D3, Lactobacillus acidophilus, and Lactobacillus casei in the 4T1 mouse model of breast cancer: anticancer and enteroprotective effects.

The use of doxorubicin (Dox) in the treatment of breast cancer negatively affects the intestines and other tissues. Many studies have proven that probiotics and vitamin D3 have antitumor and intestinal tissue-protecting properties. To achieve effectiveness and minimize side effects, the current study aims to administer Dox together with probiotics (Lactobacillus acidophilus and Lactobacillus casei) and vitamin D3. Forty-two female BALB/c inbred mice were divided into six groups: Group 1 (Control), Group 2 (Dox), Group 3 (Dox and probiotics), Group 4 (Dox and vitamin D3), Group 5 (Dox, probiotics, and vitamin D3), and Group 6 (probiotics and vitamin D3). The 4T1 mouse carcinoma cell line was injected into the mammary fat pad of each mouse. Gene expression was examined using quantitative real-time PCR. The treated groups (except group 6) showed significantly reduced tumor volume and weight compared to the control group (P < 0.05, P < 0.01). Probiotics/vitamin D3 with Dox reduced chemotherapy toxicity and a combination of supplements had a significant protective effect against Dox (P < 0.05, 0.01, 0.001). The treated groups (except 6) had significantly higher expression of Bax/Caspase 3 genes and lower expression of Bcl-2 genes than the control group (P < 0.05, 0.01). Coadministration of Dox with probiotics and vitamin D3 showed promising results in reducing tumor size, protecting intestinal tissue and influencing gene expression, suggesting a strategy to enhance the effectiveness of breast cancer treatment while reducing side effects.

Promising Anticancer Prodrugs Based on Pt(IV) Complexes with Bis-organosilane Ligands in Axial Positions.

We report two novel prodrug Pt(IV) complexes with bis-organosilane ligands in axial positions: cis-dichloro(diamine)-trans-[3-(triethoxysilyl)propylcarbamate]platinum(IV) (Pt(IV)-biSi-1) and cis-dichloro(diisopropylamine)-trans-[3-(triethoxysilyl) propyl carbamate]platinum(IV) (Pt(IV)-biSi-2). Pt(IV)-biSi-2 demonstrated enhanced in vitro cytotoxicity against colon cancer cells (HCT 116 and HT-29) compared with cisplatin and Pt(IV)-biSi-1. Notably, Pt(IV)-biSi-2 exhibited higher cytotoxicity toward cancer cells and lower toxicity on nontumorigenic intestinal cells (HIEC6). In preclinical mouse models of colorectal cancer, Pt(IV)-biSi-2 outperformed cisplatin in reducing tumor growth at lower concentrations, with reduced side effects. Mechanistically, Pt(IV)-biSi-2 induced permanent DNA damage independent of p53 levels. DNA damage such as double-strand breaks marked by histone gH2Ax was permanent after treatment with Pt(IV)-biSi-2, in contrast to cisplatin's transient effects. Pt(IV)-biSi-2's faster reduction to Pt(II) species upon exposure to biological reductants supports its superior biological response. These findings unveil a novel strategy for designing Pt(IV) anticancer prodrugs with enhanced activity and specificity, offering therapeutic opportunities beyond conventional Pt drugs.

Unlocking Overexpressed Membrane Proteins to Guide Breast Cancer Precision Medicine.

Breast cancer (BC) is a prevalent form of cancer affecting women worldwide. However, the effectiveness of current BC drugs is limited by issues such as systemic toxicity, drug resistance, and severe side effects. Consequently, there is an urgent need for new therapeutic targets and improved tumor tracking methods. This study aims to address these challenges by proposing a strategy for identifying membrane proteins in tumors that can be targeted for specific BC therapy and diagnosis. The strategy involves the analyses of gene expressions in breast tumor and non-tumor tissues and other healthy tissues by using comprehensive bioinformatics analysis from The Cancer Genome Atlas (TCGA), UALCAN, TNM Plot, and LinkedOmics. By employing this strategy, we identified four transcripts (LRRC15, EFNA3, TSPAN13, and CA12) that encoded membrane proteins with an increased expression in BC tissue compared to healthy tissue. These four transcripts also demonstrated high accuracy, specificity, and accuracy in identifying tumor samples, as confirmed by the ROC curve. Additionally, tissue microarray (TMA) analysis revealed increased expressions of the four proteins in tumor tissues across all molecular subtypes compared to the adjacent breast tissue. Moreover, the analysis of human interactome data demonstrated the important roles of these proteins in various cancer-related pathways. Taken together, these findings suggest that LRRC15, EFNA3, TSPAN13, and CA12 can serve as potential biomarkers for improving cancer diagnosis screening and as suitable targets for therapy with reduced side effects and enhanced efficacy.

Phytotherapeutic Effects of Ashanti Pepper and Horn of Plenty in Sleep Disorder Management Resulting from Stress-Induced Neurobehavioral Alterations

This investigation explores the potential antidepressant effects arising from the inherent bioactive compounds found in &amp;lt;i&amp;gt;Cnestis ferruguinea&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;Piper guineense&amp;lt;/i&amp;gt;. Both botanical entities contain flavonoids, phenolics, saponins, and tannins, which are known for their anxiolytic, antidepressant, and antioxidant properties. It is worth noting that &amp;lt;i&amp;gt;Cnestis ferruguinea&amp;lt;/i&amp;gt; also contains terpenoids, which are recognized for their anxiolytic effects. Given the growing interest in nutritional interventions for neuropsychiatric conditions, our study meticulously examines the antioxidant capacities and anxiolytic properties of these phytochemicals, positioning them as potential regulators of brain health, particularly in the realm of sleep disorders. In response to the increasing demand for therapeutic alternatives with reduced side effects, our inquiry thoroughly examines the antioxidant and anxiolytic profiles of these botanical extracts. Of particular importance, &amp;lt;i&amp;gt;Cnestis ferruguinea&amp;lt;/i&amp;gt; exhibits superior antioxidant potential compared to &amp;lt;i&amp;gt;Piper guineense&amp;lt;/i&amp;gt;, thus warranting further investigation into its pharmacological utility. Subsequent analysis of the effects of &amp;lt;i&amp;gt;Cnestis ferruguinea&amp;lt;/i&amp;gt; on sleep architecture, especially in the context of chronic stress, reveals promising results. The botanical extract significantly prolongs sleep duration in rats exposed to stress, suggesting a potential dual role in mitigating stress-induced neurobehavioral changes and depressive symptoms. Additionally, a noticeable decrease in immobility duration in the forced swim test, along with improvements in acetylcholinesterase levels following &amp;lt;i&amp;gt;Cnestis ferruguinea&amp;lt;/i&amp;gt; treatment, provides mechanistic insights into its antidepressant effects. Our findings provide substantial evidence to support the pharmacotherapeutic potential of &amp;lt;i&amp;gt;Cnestis ferruguinea&amp;lt;/i&amp;gt;, highlighted by its antioxidant abilities and anxiolytic effects. Further investigations should delve into the intricate molecular pathways underlying these effects, potentially paving the way for innovative botanical-based interventions in neuropsychiatric disorders, particularly those associated with stress-induced neurobehavioral changes and sleep disorders.

The Potential Strategies for Overcoming Multidrug Resistance and Reducing Side Effects of Monomer Tubulin Inhibitors for Cancer Therapy.

Tubulin is an essential target in tumor therapy, and this is attributed to its ability to target MT dynamics and interfere with critical cellular functions, including mitosis, cell signaling, and intracellular trafficking. Several tubulin inhibitors have been approved for clinical application. However, the shortcomings, such as drug resistance and toxic side effects, limit its clinical application. Compared with single-target drugs, multi-target drugs can effectively improve efficacy to reduce side effects and overcome the development of drug resistance. Tubulin protein degraders do not require high concentrations and can be recycled. After degradation, the protein needs to be resynthesized to regain function, which significantly delays the development of drug resistance. Using SciFinder® as a tool, the publications about tubulin-based dual-target inhibitors and tubulin degraders were surveyed with an exclusion of those published as patents. This study presents the research progress of tubulin-based dual-target inhibitors and tubulin degraders as antitumor agents to provide a reference for developing and applying more efficient drugs for cancer therapy. The multi-target inhibitors and protein degraders have shown a development prospect to overcome multidrug resistance and reduce side effects in the treatment of tumors. Currently, the design of dual-target inhibitors for tubulin needs to be further optimized, and it is worth further clarifying the detailed mechanism of protein degradation.

The Therapeutic Effects of Withaferin A against Cancer: Overview and Updates.

Cancer is a rapidly rising health problem among the global population, and this burden causes a significant challenge for public health. Current chemotherapeutic agents have different limitations, including drug resistance and severe side effects, and it demands a robust approach to accessing promising anti-cancer therapeutics. The natural compounds have been extensively studied to identify improved therapeutic agents for cancer therapy. Withaferin A (WA) is a steroidal lactone found in Withania somnifera and possesses anti-inflammatory, antioxidant, anti-angiogenesis, and anticancer properties. Multiple studies have shown that WA treatment attenuated various cancer hallmarks by inducing apoptosis and reducing angiogenesis and metastasis with reduced side effects. WA is a promising agent for the treatment of various cancer, and it targets various signaling pathways. With recent updates, the current review highlights the therapeutic implications of WA and its molecular targets in different cancer.

Hybridized quantum dot, silica, and gold nanoparticles for targeted chemo-radiotherapy in colorectal cancer theranostics

Multimodal nanoparticles, utilizing quantum dots (QDs), mesoporous silica nanoparticles (MSNs), and gold nanoparticles (Au NPs), offer substantial potential as a smart and targeted drug delivery system for simultaneous cancer therapy and imaging. This method entails coating magnetic GZCIS/ZnS QDs with mesoporous silica, loading epirubicin into the pores, capping with Au NPs, PEGylation, and conjugating with epithelial cell adhesion molecule (EpCAM) aptamers to actively target colorectal cancer (CRC) cells. This study showcases the hybrid QD@MSN-EPI-Au-PEG-Apt nanocarriers (size ~65 nm) with comprehensive characterizations post-synthesis. In vitro studies demonstrate the selective cytotoxicity of these targeted nanocarriers towards HT-29 cells compared to CHO cells, leading to a significant reduction in HT-29 cell survival when combined with irradiation. Targeted delivery of nanocarriers in vivo is validated by enhanced anti-tumor effects with reduced side effects following chemo-radiotherapy, along with imaging in a CRC mouse model. This approach holds promise for improved CRC theranostics.

Nanoparticle/Engineered Bacteria Based Triple-Strategy Delivery System for Enhanced Hepatocellular Carcinoma Cancer Therapy.

New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo. In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model. The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention. The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy.

Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom.

Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.). Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects. In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay. The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells. It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.

Effects of metalation on the PDT activity of arene ruthenium porphyrin-based photosensitizers on prostate cancer

SignificanceProstate cancer is a major health issue (second most common cancer in men worldwide). Despite therapeutic advances and early detection, many side effects are often observed during treatment. Photodynamic therapy (PDT) is a promising therapy to reduce side effects, many 2nd and 3rd generation of photosensitizer (PS) are poorly soluble in aqueous media, limiting their attractiveness. ApproachWe have developed and tested 3rd generation of PS vectorized by arene-ruthenium (Ru) complexes coordinated to tetrapyridylporphin (tpp-2H), Zn-tetrapyridylporphin (tpp-Zn) or Co-tetrapyridylporphin (tpp-Co). ResultsTwo of the three complexes show a good efficacy. The compounds localize into the cytoplasm. An analysis of the apoptotic process shows a cleavage of poly-ADP ribose polymerase (PARP) and a strong induction of DNA fragmentation following irradiation. ConclusionsArene-ruthenium tetrapyridylporphin complexes are excellent candidates for PDT application. The addition of the metal shows a decrease (tpp-Zn) or no effects (tpp-Co), compared to the metal free photosentizer (tpp-2H).

An ambispective observational study on antibiotics in pulmonology department in a tertiary care hospital

Background: Respiratory tract infections (RTIs) caused by various viruses and bacteria are a major cause of morbidity and mortality worldwide. Although they are usually more severe in children, the elderly and people with weakened immune systems, people of all ages and backgrounds are susceptible to these infections. Antibiotics are commonly prescribed for RTIs in primary care in adults and children. The main purpose of this study is to monitor the use of different antibiotics for respiratory infections. Methods: It is an ambispective observational study, during which data are collected on specially designed data collection forms. The study lasted 6 months (from December 2022 to May 2023). Results: The source of data is a total of 100 patients who were prescribed at least one dose of antibiotics. Out of 100 people, 53% were men and 47% were women. LRTI and URTI are the most common conditions for which antibiotics are prescribed, and we found that the most commonly prescribed antibiotics are a higher percentage of patients using cephalosporins. Of the various cephalosporins, the most commonly prescribed is ceftriaxone, a third-generation cephalosporin. Conclusions: From this particular observational study, we concluded that the most frequently prescribed antibiotics for respiratory infections were cephalosporins, ceftriaxone, third-generation cephalosporins were most frequently prescribed, followed by macrolides, penicillin, tetracyclines, lincomycin, fluoroquinolones, oxazolidinones. The use of antibiotics helps to improve patient care by reducing side effects such as antibiotic resistance, hypersensitivity reactions, respiratory difficulties and risks associated with respiratory infections.

Lipid-based nanoparticles and their recent advances

Lipid-based nanoparticles hold great potential for drug delivery, providing biocompatibility and the ability to encapsulate both hydrophilic and hydrophobic drugs. However, there are certain challenges associated with small molecules, such as leakage and premature release, which can compromise their effectiveness. Despite these challenges, lipid nanoparticles offer advantages in terms of solubility, stability, and targeted delivery, thereby reducing side effects. Additionally, they can be customized for specific molecules, ensuring biocompatibility and biodegradability. While complications may arise, lipid nanoparticles offer numerous benefits for loading biomolecules, improving pharmacokinetics, and enhancing therapeutic effects. It is important to address stability and loading challenges when encapsulating biomolecules and consider potential immunogenic responses that may impact biocompatibility and safety.