Severe Side Effects Research Articles

Regulation of tumor antigens-Dependent immunotherapy via the hybrid M1 macrophage/tumor lysates Hydrogel

Tumor treatment poses a significant obstacle in contemporary healthcare. Using components derived from a patient's own cellular and tissue materials to prepare hydrogels and other therapeutic systems has become a novel therapeutic approach, drawing considerable interest for their applicability in basic research on cancer immunotherapy. These hydrogels can engage with cellular components directly and offer a supportive scaffold, aiding in the normalization of tumor tissues. Additionally, their superior capability for encapsulating targeted anti-tumor medications amplifies treatment effectiveness. Given their origin from a patient's own cells, these hydrogels circumvent the risks of immune rejection by the body and severe side effects typically associated with foreign substance. In this study, we developed a composite hydrogel constructed by the cellular lysates of autologous tumor cells and M1 macrophages. This combination promoted the M2 macrophages polarization to the M1 phenotype. Subsequently, the polarized M1 macrophages infiltrated into the hydrogel and can directly capture tumor antigens. As antigen-presenting cells, M1 macrophages can stimulate the production of antigen-specific T cells to kill tumor cells. This work proposes a dual-benefit research strategy that not only polarizes M2 macrophages but also enhances immune activation, boosting T cell-mediated tumor-killing effects. This approach offers a new therapeutic option for clinical cancer immunotherapy.

Electrochemistry of different ruthenium polypyridine complexes

In search for antitumor metal-based drugs that would mitigate the severe side-effects of cisplatin, Ru(II) complexes are gaining increasing recent interest. Their cytotoxic effect is widely known, however mechanism of action, solution behavior, redox reactions within biological system are still focus of the new studies. Various experiments and approach techniques are used to better understand ruthenium chemistry. In this order their biological activity and the availability of reduction potential in the biological medium, it is necessary to know their electrochemical redox behavior and properties. In this work, we report the electrochemical activity on synthesized and characterized (1H- and 13C NMR, FT-IR, MS) half-sandwich organometallic Ru(II) complexes of the general formula [Ru(η6-arene)(XY)Cl](PF6) where arene = benzene, toluene or p-cymene and XY = bidentates: dipyrido[3,2-a:2′,3′-c]phenazine (dppz derivatives) or 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip), which are bound to Ru(II) via two phenanthroline-N atoms in a characteristic “piano-stool” configuration of Ru(II)-arene complexes – as confirmed by vibrational and NMR spectra. It is shown that selected complexes can be divided in four groups, based on their electrochemical behavior. These behaviors are correlated with their structure and nature of ligands.

Effect of Agkistrodon acutus venom (AAVC-I) on apoptosis through modulation of the Keap1/Nrf2 pathway in HSC-3 oral squamous cell carcinoma cells.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions. Patients with OSCC exhibit a poor response to conventional chemoradiotherapies, which are associated with severe side effects. Therefore, it is essential to identify an effective therapeutic method to treat patients with OSCC. An anti-tumor compound, Agkistrodon acutus venom component I (AAVC-I), purified from Agkistrodon acutus venom, has demonstrated anticancer activity both in vitro and in vivo. However, the mechanism of AAVC-I's anticancer activity in cancer cells has yet to be established. This study aimed to investigate the mechanism of AAVC-I-induced apoptosis in HSC-3 OSCC cells and explore its regulatory effect on oxidative stress. Survival rates of human OSCC cell HSC-3 were detected by Cell Counting Kit-8 (CCK-8). The reactive oxygen species (ROS) level was analyzed by flow cytometry and fluorescence microscopy. The mitochondrial membrane potential was analyzed by cytometry and fluorescent microplate reader. Apoptosis of HSC-3 cells was analyzed using flow cytometry. The oxidative stress level was evaluated using glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits. In addition, the target proteins were analyzed by western blot. AAVC-I reduced HSC-3 cells' survival rates in a dose-dependent manner with a 50% inhibiting concentration (IC50) of 8.86 µg/mL. It induced apoptosis of HSC-3 cells and the expression of cleaved caspase-3, cleaved caspase-9, and Cyt-c increased significantly, whereas the expression level of Bcl-2 decreased in AAVC-I-treated HSC-3 cells. Thus, AAVC-I caused apoptosis of HSC-3 via the activation of the intrinsic apoptotic pathway. In addition, AAVC-I reduced the mitochondrial membrane potential in HSC-3, enhanced intracellular ROS, and increased intracellular oxidative stress levels in comparison to that of untreated control cells. Furthermore, AAVC-I increased the expression of Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) levels. These findings demonstrate the inhibitory effects and associated mechanisms of AAVC-I on the HSC-3 OSCC cell line. This insight could be valuable for investigating AAVC-I as a potential therapeutic option for patients with OSCC.

Prognostic role of dynamic changes in inflammatory indicators in patients with non-small cell lung cancer treated with immune checkpoint inhibitors-a retrospective cohort study.

Immune checkpoint inhibitors (ICIs) have become one of the standard treatments for non-small cell lung cancer (NSCLC) patients without driver mutations. However, a considerable proportion of patients suffer from severe immune side effects and fail to respond to ICIs. As effective biomarkers, programmed cell death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) require invasive procedures that place heavy physical and psychological burdens on patients. This study aims to identify simple and effective markers to optimize patient selection through therapeutic decisions and outcome prediction. This retrospective study comprised 95 patients with metastatic NSCLC who were treated with ICIs either as the standard of care or in a clinical trial. The following data were extracted from the medical records. The baseline and dynamic neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated in the present study. Responses were assessed by computed tomography (CT) imaging and classified according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6-12 weeks during treatment. In total, 95 patients were included in the present study. The median age of patients was 61 years, 83.2% (79/95) patients were male, 62.1% (59/95) were former or current smokers, 66.3% (63/95) had adenocarcinoma, 93.7% (89/95) had stage IV disease, and 87.4% were without molecular alterations. A higher overall response rate (ORR) and prolonged median progression-free survival (PFS) was observed in patients with a lower cycle 3 (C3) NLR [7.7 vs. 5.5 months, hazard ratio (HR): 1.70, 95% confidence interval (CI): 0.90-3.22; P=0.12] and derived NLR (dNLR) (8.2 vs. 5.6 months, HR: 1.67, 95% CI: 0.94-2.97; P=0.08). After two cycles of ICI treatment, patients who had an increased NLR, dNLR, and PLR had a lower ORR and an inferior median PFS than those with a decreased NLR (5.5 vs. 8.5 months, HR: 1.87, 95% CI: 1.09-3.21; P=0.02), dNLR (5.6 vs. 8.4 months, HR: 1.49, 95% CI: 0.87-2.57; P=0.15), and PLR (11.8 vs. 5.5 months, HR: 2.28, 95% CI: 1.32-3.94; P=0.003). Moreover, patients with both an increased NLR and PLR had a worse ORR and median PFS than those with either an increased NLR or PLR, or both an increased NLR and PLR (11.8 vs. 5.5 vs. 5.6 months, P=0.003). In addition, the dynamic changes in the PLR could serve as an independent predictive factor of PFS in NSCLC patients treated with ICIs. Elevated dynamic changes in the NLR and PLR were associated with lower response rates and shorter PFS in the patients with NSCLC treated with ICIs. Our results also highlight the role of dynamic changes in the PLR in identifying patients with NSCLC who could benefit from ICIs.

Protective Effects of Spermacoce hispida Against Cisplatin-Induced Nephrotoxicity: A Study on Oxidative and Nitrosative Stress

Background: Nephrotoxicity is a common and severe side effect of cisplatin, a widely used chemotherapeutic agent. The mechanism of cisplatin-induced nephrotoxicity involves oxidative stress, inflammation, and apoptosis, leading to renal damage. There is growing interest in exploring natural products with antioxidant and anti-inflammatory properties as potential protective agents against drug-induced nephrotoxicity.Objective: The present study aimed to investigate the protective effects of Spermacoce hispida against cisplatin-induced nephrotoxicity in an in vivo rat model. Methods: S. hispida was collected, and plant extracts were prepared using different solvents. The prepared extracts underwent phytochemical screening. Nephrotoxicity was induced in rats through a single intraperitoneal injection of cisplatin at a dose of 5 mg/kg. S. hispida extracts at a dose of 100 mg/kg were administered to assess their protective activity. Key parameters measured included blood urea nitrogen (BUN), serum creatinine, oxidative stress markers, proinflammatory cytokines, nitric oxide (NO) levels, and histological alterations in kidney tissue.Results: Cisplatin treatment resulted in increased levels of BUN, serum creatinine, and proinflammatory cytokines in rats, indicating nephrotoxicity. However, treatment with S. hispida extracts for 14 days significantly decreased these elevated levels. Additionally, S. hispida treatment reduced oxidative stress and NO production in cisplatin-treated rats. Histological examination revealed that cisplatin induced structural damage in kidney tissues, which was normalized by S. hispida treatment. Conclusion: The study concludes that Spermacoce hispida exhibits nephroprotective activity, likely by inhibiting oxidative stress and NO production, thereby mitigating cisplatin-induced nephrotoxicity in rats

Comparative analysis of Paiteling a traditional Chinese medicine (TCM) and CO2 laser therapy for high-risk HPV-associated with LSIL (CIN1) lesions

ObjectivesThis study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus. MethodsWe retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient’s results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy. ResultsThe median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26–6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92–22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6–12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6–12 months: p < 0.010, 12–18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers.The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix. ConclusionsPaiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation.

The preventive effect of photocrosslinked Hep/GelMA hydrogel loaded with PRF on MRONJ.

Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ.

Patient Preferences for First-Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma: An Application of Multidimensional Thresholding.

Patient preferences have the potential to influence the development of new treatments for locally advanced/metastatic urothelial carcinoma (la/mUC), and therefore we explored how patients with la/mUC value different attributes of first-line treatments. An online preference survey and multidimensional thresholding (MDT) exercise were developed following a targeted literature review and qualitative interviews with physicians, patients with la/mUC, and their caregivers. Treatment attributes included two benefits (overall response rate [ORR], pain related to bladder cancer [scored 0-100; 100 being the worst pain possible]) and four treatment-related risks (peripheral neuropathy, severe side effects, mildtomoderate nausea, mildtomoderate skin reactions). A Dirichlet regression was used to estimate average preference weights. Marginal utility and the reduction in ORR that patients would accept in exchange for a 10-pointdecrease or a10% decrease in other attributes were calculated. A total of 100 patients were recruited and self-completed the survey and MDT. Mean patient age was 64.9 years (standard deviation, 7.6), 54% were female, and 38% identified as white. All included treatment attributes had a statistically significant impact on preferences. Changes in ORR had the largest impact, followed by cancer-related pain and treatment-related risks. Patients were willing to accept an 8.4% decrease in ORR to reduce their pain level by 10 points or a 7.8% decrease in ORR to reduce the risk of peripheral neuropathy by 10%. For a 10% decrease in severe side effects, mildtomoderate nausea, or skin reaction, patients would accept decreases in ORR of 5.5%, 3.7%, or 3.4%, respectively. Of the attributes tested, changes in ORR were most important to patients. Patients made tradeoffs between treatment attributes indicating that a lower ORR may be acceptable for an improvement in other attributes such as reduced cancer-related pain or the risk of treatment-related adverse events.

Nanomaterial-based therapeutics for enhanced antifungal therapy.

The application of nanotechnology in antifungal therapy is gaining increasing attention. Current antifungal drugs have significant limitations, such as severe side effects, low bioavailability, and the rapid development of resistance. Nanotechnology offers an innovative solution to address these issues. This review discusses three key strategies of nanotechnology to enhance antifungal efficacy. Firstly, nanomaterials can enhance their interaction with fungal cells via ingenious surface tailoring of nanomaterials. Effective adhesion of nanoparticles to fungal cells can be achieved by electrostatic interaction or specific targeting to the fungal cell wall and cell membrane. Secondly, stimuli-responsive nanomaterials are developed to realize smart release of drugs in the specific microenvironment of pathological tissues, such as the fungal biofilm microenvironment and inflammatory microenvironment. Thirdly, nanomaterials can be designed to cross different physiological barriers, effectively addressing challenges posed by skin, corneal, and blood-brain barriers. Additionally, some new nanomaterial-based strategies in treating fungal infections are discussed, including the development of fungal vaccines, modulation of macrophage activity, phage therapy, the application of high-throughput screening in drug discovery, and so on. Despite the challenges faced in applying nanotechnology to antifungal therapy, its significant potential and innovation open new possibilities for future clinical antifungal applications.

First-line Chemotherapy in Combination With Oral Recombinant Methioninase and a Low-methionine Diet for a Stage IV Inoperable Pancreatic-Cancer Patient Resulted in 40% Tumor Reduction and an 86% CA19-9 Biomarker Decrease.

Pancreatic cancer has a very poor prognosis with a 5-year survival rate of less than 5% among patients with distant metastasis, a figure that has not improved over many decades. Only 10 to 20% patients are candidates for curative surgery at presentation due to the aggressive nature and asymptomatic progression of pancreatic cancer. Although first-line chemotherapy, such as FOLFIRINOX and gemcitabine + nab paclitaxel, improved the median survival from 8.5 to 11.1 months, more effective treatments are immediately needed. The aim of the present study was to evaluate the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet combined with first-line chemotherapy on a patient with stage IV metastatic pancreatic cancer. A 63-year-old female was diagnosed with metastatic pancreatic cancer in October 2023. The patient started FOLFIRINOX as first-line chemotherapy in combination with methionine restriction, which comprised o-rMETase 250 units twice a day and a low-methionine diet. The patient was monitored using computed tomography and CA19-9 blood tests. After five months from the start of combination therapy, the size of the primary tumor decreased by 40% along with liver-metastasis regression. The CA19-9 blood marker decreased by 86%. The patient sustains a high performance status and continues the combination therapy without severe side effects. Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with first-line chemotherapy, was highly effective in a patient with inoperable stage IV pancreatic cancer.

Natural products: A potential immunomodulators against inflammatory-related diseases.

The incidence and prevalence of inflammatory-related diseases (IRDs) are increasing worldwide. Current approved treatments for IRDs in the clinic are combat against inhibiting the pro-inflammatory cytokines. Though significant development in the treatment in the IRDs has been achieved, the severe side effects and inefficiency of currently practicing treatments are endless challenge. Drug discovery from natural sources is efficacious over a resurgence and also natural products are leading than the synthetic molecules in both clinical trials and market. The use of natural products against IRDs is a conventional therapeutic approach since it is a reservoir of unique structural chemistry, accessibility and bioactivities with reduced side effects and low toxicity. In this review, we discuss the cause of IRDs, treatment of options for IRDs and the impact and adverse effects of currently practicing clinical drugs. As well, the significant role of natural products against various IRDs, the limitations in the clinical development of natural products and thus pave the way for development of natural products as immunomodulators against IRDs are also discussed.

Dronabinol Is Not a Game Changer in Pediatric Palliative Care: Results from a Retrospective Study.

Patients with life-limiting conditions (LLCs) often suffer from restlessness, spasticity, pain, and seizures. Dronabinol (DRB) may have a relieving effect; however, data on the effectiveness of DRB in children with LLCs are limited to outpatients. The aim of this study was to assess the efficacy and safety of DRB. Retrospective analysis of inpatients. From 2011 to 2021, 1219 patients were admitted. Of these, 63 patients (63.5% male, age: 10.4 (SD = 6.3) years) were treated with DRB; 96.8% had a neurological disease, and 26 patients were started on DRB (group A), while 37 were admitted with existing DRB (group B). The effective doses were 0.21 (SD = 0.11) in group A and 0.48 (SD = 0.5) mg/kg/BW/day in group B (p = 0.01). Subjective response rates to DRB in both groups (good/moderate effect) were 9.5%/38.1% for spasticity and 1.6%/25.4% for restlessness. However, no reduction in seizures, restlessness, or demand medication was observed in 24 h protocols when patients started DRB in group A. Three patients experienced severe side effects (e.g., respiratory depression). Other side effects included fatigue (22.2%) and behavioral problems (14.3%). Subjective positive effects could not be confirmed by more objective data. Side effects can be severe. Thus, DRB should be started in a well-monitored setting and only with clear indications.

Advancements in Hydrogel-Based Therapies for Ovarian Cancer: A Review.

Ovarian cancer, the most deadly gynecologic malignancy, is often resistant to conventional antitumor therapy due to various factors such as severe side effects, unexpected recurrence, and significant tissue damage. The limitations of current treatments and the resistance of invasive tumor cells contribute to these challenges. Hydrogel therapy has recently emerged as a potential treatment option for ovarian cancer, offering advantages such as controllability, biocompatibility, high drug loading capacity, prolonged drug release, and responsiveness to specific stimuli. Hence, the utilization of biodegradable hydrogels as carriers for chemotherapeutic agents has emerged as a significant concern in the field. Injectable hydrogel-based drug delivery systems, in particular, have demonstrated superior efficacy compared to traditional systemic chemotherapy for cancer treatment. The pliability of hydrogel therapy allows for access to anatomical regions that may be challenging for surgical intervention. This review article examines recent advancements in the application of hydrogels for diagnosing and treating ovarian cancer, while also proposing a novel direction for the use of hydrogel technology in this context. The objective of this article is to offer a novel point of reference and serve as a source of inspiration for the advancement of more precise and individualized cancer therapies.

Controlled bioorthogonal activation of Bromodomain-containing protein 4 degrader by co-delivery of PROTAC and Pd-catalyst for tumor-specific therapy

The precise and safe treatment of bioorthogonal prodrug system is hindered by separate administration of prodrug and its activator, which often results in poor therapeutic effects and severe side effects. To address above issues, we herein construct a single bioorthogonal-activated co-delivery system for simultaneous PROTAC prodrug (proPROTAC) delivery and controlled, site-specific activation for tumor-specific treatment. In this co-delivery system (termed AuPLs), prodrug (proPROTAC) and water-soluble Pd-catalyst are first encapsulated by gold nanocubes (AuNCs), which are further coated with a layer of phase-change material (lauric acid/stearic acid, LA/SA). Below 39 °C, the solid state of LA/SA prevents the activation of Pd-mediated bioorthogonal reaction due to the solidification of Pd-catalyst and proPROTAC. Nevertheless, once over 42 °C, the phase change of LA/SA into liquid state, enabled by the photothermal effect of AuNCs, triggers the simultaneous release of proPROTAC and Pd-catalyst and initiates the in situ bioorthogonal reaction for proPROTAC activation. In the tumor-bearing mouse models, the systemic administration of AuPLs results in the accumulation in tumor region, where the photothermal effect activates and controls the tumor-specific bioorthogonal reaction to degrade BRD4 protein, leading to anti-tumor effects with minimized side effects. Overall, the co-delivery proPROTAC and Pd-catalyst and controlled activation by photothermal effects provide a precise way for biorthogonal-based anticancer prodrugs.

DNA damage response-related ncRNAs as regulators of therapy resistance in cancer.

The DNA damage repair (DDR) pathway is a complex signaling cascade that can sense DNA damage and trigger cellular responses to DNA damage to maintain genome stability and integrity. A typical hallmark of cancer is genomic instability or nonintegrity, which is closely related to the accumulation of DNA damage within cancer cells. The treatment principles of radiotherapy and chemotherapy for cancer are based on their cytotoxic effects on DNA damage, which are accompanied by severe and unnecessary side effects on normal tissues, including dysregulation of the DDR and induced therapeutic tolerance. As a driving factor for oncogenes or tumor suppressor genes, noncoding RNA (ncRNA) have been shown to play an important role in cancer cell resistance to radiotherapy and chemotherapy. Recently, it has been found that ncRNA can regulate tumor treatment tolerance by altering the DDR induced by radiotherapy or chemotherapy in cancer cells, indicating that ncRNA are potential regulatory factors targeting the DDR to reverse tumor treatment tolerance. This review provides an overview of the basic information and functions of the DDR and ncRNAs in the tolerance or sensitivity of tumors to chemotherapy and radiation therapy. We focused on the impact of ncRNA (mainly microRNA [miRNA], long noncoding RNA [lncRNA], and circular RNA [circRNA]) on cancer treatment by regulating the DDR and the underlying molecular mechanisms of their effects. These findings provide a theoretical basis and new insights for tumor-targeted therapy and the development of novel drugs targeting the DDR or ncRNAs.

Highly sensitive MXene-based voltammetric sensor for nanomolar clozapine detection

Clozapine is vital for managing schizophrenia and other psychiatric disorders. As a potent medication with risks of severe side effects, accurate detection ensures effective treatment monitoring, patient safety, and optimization of therapeutic outcomes. Herein, niobium carbide two-dimensional transition metal carbides (Nb2CTx MXene) was prepared by etching niobium aluminum carbide (Nb2AlC), which was next partially oxidized by a hydrothermal method to niobium oxide (Nb2O5)/Nb2CTx and ultrasonically bound to carboxylated multi-walled carbon nanotubes (MWCNTs-COOH). It was modified onto a glassy carbon electrode for the detection of the antipsychotic drug clozapine ingested by humans. The morphology and electrochemical properties of MXene-based nanocomposite electrode were verified by scanning electron microscopy, X-ray diffractometry, Raman, cyclic voltammetry and electrochemical impedance characterization methods. The results showed that electrode responded well to clozapine solutions, with good linearity (R2 = 0.9979 and 0.9995) of the peak currents with clozapine concentrations (0.01–1.0 μM and 1.0–10.0 μM) and that this sensor had good immunity, repeatability, reproducibility and stability. The limit of detection was 8.38 nM and the recovery was 92.5 % ~ 106.5 % in real serum and urine samples. The MXene-based sensors offer excellent analytical performance and hold promise for cost-effective generalisation to the detection of nanomolar clozapine in a variety of clinical applications.

Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo-Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury.

In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen-treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation-targeting prowess while sidestepping the release of pro-inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid-loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy "Trojan horse" in the battle against pneumonia-induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.

Nano-Medicine for Treatment of Tuberculosis, Promising Approaches Against Antimicrobial Resistance.

Even though the number of effective anti-tuberculosis or anti-mycobacterial agents is increasing, a large number of patients experience severe side effects as a result of these drugs. This hurts the patients' well-being and quality of life. Tumor cells that survive treatment modalities can become chemotherapy resistant at the molecular level. Furthermore, negative effects on normal cells occur concurrently. Strategies that minimize the negative effects on normal cells while efficiently targeting infected cells are required. Nanotherapies, according to recent research, may be one option in this direction. The present study differs from previously published review studies as it concentrates on examining the most recently developed nanoparticles for anti-mycobacterial purposes. Such novel approaches have the potential to reduce harmful side effects and improve patients' health prognoses.Current paper provides a comprehensive analysis of recent advances in nanotherapy systems for the pulmonary delivery of anti-tuberculous drugs. In addition, to low-priced and convenient alternatives for pulmonary delivery, different types of NPs for oral and topical application were also deliberated and summarized in this review.

Unveiling the anticancer potential of Pestalotioprolide E, an unexplored macrolide: Targeting TRXR1-TRX1-ASK1-P38 signaling cascade in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is highly aggressive and metastatic in nature. Existing treatment modalities for TNBC are associated with severe side effects. Thioredoxin reductase (TRXR), the pivotal component of the thioredoxin system, remains overexpressed in various cancer cells including TNBC; promotes cell growth, proliferation, and metastasis, and inhibits apoptosis. Pestalotioprolide E is one of the potent macrolides, a class of secondary metabolites derived from an endophytic fungus Pestalotiopsis microspora with relatively unexplored biological activities. Our study revealed increased expression and activity of TRXR1 in MDA-MB-231 cells compared to the non-cancerous cells. In silico docking analysis and in vitro activity assay demonstrated that Pestalotioprolide E directly interacts with TRXR1 and inhibits its enzymatic activity. This inhibition induces apoptosis via TRX1/ASK1/P38MAPK death signaling cascade and retards metastasis through modulating VEGF, MMP-2, MMP-9, E-cadherin, N-cadherin in MDA-MB-231 cells. Taken together present study establishes TRXR1 as a molecular target for Pestalotioprolide E and its anticancer effect can be attributed to the inhibition of TRXR1 activity in MDA-MB-231.

Hybrid cell membranes camouflage liposomes containing payloads to improve breast cancer chemo and photodynamic therapy.

The treatment of unresectable locally advanced triple-negative breast cancer (TNBC) and TNBC with metastasis is challenging. Many anticancer drugs, such as doxorubicin, still hinder positive therapeutic outcomes due to severe side effects. Photodynamic therapy (PDT) has an anticancer effect, and combining PDT with chemotherapy may improve breast cancer therapy. The use of cargo-loaded biomimetic PEGylated liposomes for cancer therapy may enhance efficacy and reduce side effects. In this study, liposomes were formulated to accommodate doxorubicin (Dox) and IR780. Breast cancer cells (4T1 cells) and macrophage cell membranes were isolated and camouflaged onto the PEGylated liposomes, creating a new biomimetic platform called Dox-IR780@Lip@Ms. The Dox-IR780@Lip@Ms platform was characterized and tested in vitro and in vivo. The results showed that the Dox-IR780@Lip@Ms had an ovoid shape with a double lamina structure, monodispersity, and uniform distribution. The size was 132.37 ± 1.22 nm, the PDI was 0.044 ± 0.067, and the zeta potential was -9.67 ± 1.08 mV. The encapsulation efficiency of Dox and IR780 in Dox-IR780@Lip@Ms was 89.36% ± 3.07% and 92.34% ± 0.66%, respectively. The release rate of Dox from Dox-IR780@Lip@Ms was good after laser irradiation. At pH 7.4, the release rate of Dox was 23.85% ± 0.62% at 3 h without laser irradiation and 36.62% ± 1.32% at 3.5 h with laser irradiation. At pH 6.5, the release rate of Dox was 32.54% ± 0.32% at 3 h without laser irradiation and 62.79% ± 2.15% at 3.5 h with laser irradiation. The cytotoxicity of IR780@Lip@Ms was lower than that of Dox-IR780@Lip@Ms. The cell uptake and generation of reactive oxygen species of Dox-IR780@Lip@Ms were significant. Dox-IR780@Lip@Ms exhibited immune escaping ability in vitro, homotypic targeting ability to cancer cells, high capability to kill cancer cells after laser irradiation, minimal cardiotoxicity, increased accumulation of Dox and IR780 in the tumor, and an increased anticancer effect in a tumor-bearing animal model. In conclusion, hybrid cell membranes of breast cancer and macrophages camouflaging PEGylated liposomes loaded with Dox and IR780 can significantly improve breast cancer therapy after laser irradiation in murine models.