The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-known regulator of cholesterol metabolism and cardiovascular diseases, has recently garnered attention for its emerging involvement in cancer biology. The multifunctional nature of PCSK9 extends beyond lipid regulation and encompasses a wide range of cellular processes that can influence cancer progression. Studies have revealed that PCSK9 can modulate signaling pathways, such as PI3K/Akt, MAPK, and Wnt/ß-catenin, thereby influencing cellular proliferation, survival, and angiogenesis. Additionally, the interplay between PCSK9 and cholesterol homeostasis may impact membrane dynamics and cellular migration, further influencing tumor aggressiveness. The central role of the immune system in monitoring and controlling cancer is increasingly recognized. Recent research has demonstrated the ability of PCSK9 to modulate immune responses through interactions with immune cells and components of the tumor microenvironment. This includes effects on dendritic cell maturation, T cell activation, and cytokine production, suggesting a role in shaping antitumor immune responses. Moreover, the potential influence of PCSK9 on immune checkpoints such as PD1/PD-L1 lends an additional layer of complexity to its immunomodulatory functions. The growing interest in cancer immunotherapy has prompted exploration into the potential of targeting PCSK9 for therapeutic benefits. Preclinical studies have demonstrated synergistic effects between PCSK9 inhibitors and established immunotherapies, offering a novel avenue for combination treatments. The strategic manipulation of PCSK9 to enhance tumor immunity and improve therapeutic outcomes presents an exciting area for further investigations. Understanding the mechanisms by which PCSK9 influences cancer biology and immunity holds promise for the development of novel immunotherapeutic approaches. This review aims to provide a comprehensive analysis of the intricate connections between PCSK9, cancer pathogenesis, tumor immunity, and the potential implications for immunotherapeutic interventions.

Berberine and berberine nanoformulations in cancer therapy: Focusing on lung cancer.

Lung cancer is the second most prevalent cancer and ranks first in cancer-related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p-glycoprotein-dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)-based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal-based NPs, carbon nanostructures, and others, in the treatment of lung cancer.

Interleukin-6 serves as a critical factor in various cancer progression and therapy.

Interleukin-6 (IL-6), a pro-inflammatory cytokine, plays a crucial role in host immune defense and acute stress responses. Moreover, it modulates various cellular processes, including proliferation, apoptosis, angiogenesis, and differentiation. These effects are facilitated by various signaling pathways, particularly the signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). However, excessive IL-6 production and dysregulated signaling are associated with various cancers, promoting tumorigenesis by influencing all cancer hallmarks, such as apoptosis, survival, proliferation, angiogenesis, invasiveness, metastasis, and notably, metabolism. Emerging evidence indicates that selective inhibition of the IL-6 signaling pathway yields therapeutic benefits across diverse malignancies, such as multiple myeloma, prostate, colorectal, renal, ovarian, and lung cancers. Targeting key components of IL-6 signaling, such as IL-6Rs, gp130, STAT3, and JAK via monoclonal antibodies (mAbs) or small molecules, is a heavily researched approach in preclinical cancer studies. The purpose of this study is to offer an overview of the role of IL-6 and its signaling pathway in various cancer types. Furthermore, we discussed current preclinical and clinical studies focusing on targeting IL-6 signaling as a therapeutic strategy for various types of cancer.

Advances in chitosan-based blends as potential drug delivery systems: A review.

During the last decades, the ever-increasing incidence of diseases has led to high rates of mortality throughout the world. On the other hand, the inability and deficiencies of conventional approaches (such as chemotherapy) in the suppression of diseases remain challenging issues. As a result, there is a fundamental requirement to develop novel, biocompatible, bioavailable, and practical nanomaterials to prevent the incidence and mortality of diseases. Chitosan (CS) derivatives and their blends are outstandingly employed as promising drug delivery systems for disease therapy. These biopolymers are indicated more efficient performance against diseases compared with conventional modalities. The CS blends possess improved physicochemical properties, ease of preparation, high affordability, etc. characteristics compared with other biopolymers and even pure CS which result in efficient thermal, mechanical, biochemical, and biomedical features. Also, these blends can be administrated through different routes without a long-term treatment period. Due to the mentioned properties, numerous formulations of CS blends are developed for pharmaceutical sciences to treat diseases. This review article highlights the progressions in the development of CS-based blends as potential drug delivery systems against diseases.

A comprehensive insight into the contribution of epigenetics in male infertility; focusing on immunological modifications.

Numerous recent studies have examined the impact epigenetics-including DNA methylation-has on spermatogenesis and male infertility. Differential methylation of several genes has been linked to compromised spermatogenesis and/or reproductive failure. Specifically, male infertility has been frequently associated with DNA methylation abnormalities of MEST and H19 inside imprinted genes and MTHFR within non-imprinted genes. Microbial infections mainly result in male infertility because of the immune response triggered by the bacteria' accumulation of immune cells, proinflammatory cytokines, and chemokines. Thus, bacterially produced epigenetic dysregulations may impact host cell function, supporting host defense or enabling pathogen persistence. So, it is possible to think of pathogenic bacteria as potential epimutagens that can alter the epigenome. It has been demonstrated that dysregulated levels of LncRNA correlate with motility and sperm count in ejaculated spermatozoa from infertile males. Therefore, a thorough understanding of the relationship between decreased reproductive capacity and sperm DNA methylation status should aid in creating new diagnostic instruments for this condition. To fully understand the mechanisms influencing sperm methylation and how they relate to male infertility, more research is required.

Exploring the impact of circRNAs on cancer glycolysis: Insights into tumor progression and therapeutic strategies.

Cancer cells exhibit altered metabolic pathways, prominently featuring enhanced glycolytic activity to sustain their rapid growth and proliferation. Dysregulation of glycolysis is a well-established hallmark of cancer and contributes to tumor progression and resistance to therapy. Increased glycolysis supplies the energy necessary for increased proliferation and creates an acidic milieu, which in turn encourages tumor cells' infiltration, metastasis, and chemoresistance. Circular RNAs (circRNAs) have emerged as pivotal players in diverse biological processes, including cancer development and metabolic reprogramming. The interplay between circRNAs and glycolysis is explored, illuminating how circRNAs regulate key glycolysis-associated genes and enzymes, thereby influencing tumor metabolic profiles. In this overview, we highlight the mechanisms by which circRNAs regulate glycolytic enzymes and modulate glycolysis. In addition, we discuss the clinical implications of dysregulated circRNAs in cancer glycolysis, including their potential use as diagnostic and prognostic biomarkers. All in all, in this overview, we provide the most recent findings on how circRNAs operate at the molecular level to control glycolysis in various types of cancer, including hepatocellular carcinoma (HCC), prostate cancer (PCa), colorectal cancer (CRC), cervical cancer (CC), glioma, non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer (GC). In conclusion, this review provides a comprehensive overview of the significance of circRNAs in cancer glycolysis, shedding light on their intricate roles in tumor development and presenting innovative therapeutic avenues.

Exploring the significance of microbiota metabolites in rheumatoid arthritis: uncovering their contribution from disease development to biomarker potential.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.

Exploiting the immune system in hepatic tumor targeting: Unleashing the potential of drugs, natural products, and nanoparticles.

Hepatic tumors present a formidable challenge in cancer therapeutics, necessitating the exploration of novel treatment strategies. In recent years, targeting the immune system has attracted interest to augment existing therapeutic efficacy. The immune system in hepatic tumors includes numerous cells with diverse actions. CD8+ T lymphocytes, T helper 1 (Th1) CD4+ T lymphocytes, alternative M1 macrophages, and natural killer (NK) cells provide the antitumor immunity. However, Foxp3+ regulatory CD4+ T cells (Tregs), M2-like tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) are the key immune inhibitor cells. Tumor stroma can also affect these interactions. Targeting these cells and their secreted molecules is intriguing for eliminating malignant cells. The current review provides a synopsis of the immune system components involved in hepatic tumor expansion and highlights the molecular and cellular pathways that can be targeted for therapeutic intervention. It also overviews the diverse range of drugs, natural products, immunotherapy drugs, and nanoparticles that have been investigated to manipulate immune responses and bolster antitumor immunity. The review also addresses the potential advantages and challenges associated with these approaches.

An electrochemical sensor for the determination of environmentally hazardous fungicide pyrimethanil in water and fruit samples.

We developed a facile electroanalytical system for the rapid and sensitive detection of pyrimethanil through the modification of carbon paste electrode surface using the as-fabricated europium doped feather-type CuO nanoflowers (FT-Eu3+-CuO NF sensor). The peak current of pyrimethanil oxidation was elevated by the sensor due to the integration of appreciable electrochemical features of the modifier, which indicates the high ability of the modified electrode to enhance the sensitivity of pyrimethanil detection. The pyrimethanil sensor under the optimized setting had a broad linear dynamic range (0.001-800.0 µM) and a narrow limit of detection (0.18 nM). The practical applicability of the as-fabricated electrode was verified by sensing pyrimethanil in real samples; it also exhibited commendable specificity, stability and reproducibility.

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.

Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health. Cancer cells possess six biological characteristics during their developmental process known as cancer hallmarks. Hallmarks of cancer include continuous growth signals, unlimited proliferation, resistance to proliferation inhibitors, apoptosis escaping, active angiogenesis, and metastasis. Sesquiterpene lactones are one of the large and diverse groups of planet-derived phytochemicals that can be used as sources for a variety of drugs. Some sesquiterpene lactones possess many biological activities such as anti-inflammatory, anti-viral, anti-microbial, anti-malarial, anticancer, anti-diabetic, and analgesic. This review article briefly overviews the intrinsic and extrinsic pathways of apoptosis and the interactions between the modulators of both pathways. Also, the present review summarizes the potential effects of sesquiterpene lactones on different modulators of the intrinsic and extrinsic pathways of apoptosis in a variety of cancer cell lines and animal models. The main purpose of the present review is to give a clear picture of the current knowledge about the pro-apoptotic effects of sesquiterpene lactones on various cancers to provide future direction in cancer therapeutics.

Chitosan-based nanofibrous scaffolds for biomedical and pharmaceutical applications: A comprehensive review.

Nowadays, there is a wide range of deficiencies in treatment of diseases. These limitations are correlated with the inefficient ability of current modalities in the prognosis, diagnosis, and treatment of diseases. Therefore, there is a fundamental need for the development of novel approaches to overcome the mentioned restrictions. Chitosan (CS) nanoparticles, with remarkable physicochemical and mechanical properties, are FDA-approved biomaterials with potential biomedical aspects, like serum stability, biocompatibility, biodegradability, mucoadhesivity, non-immunogenicity, anti-inflammatory, desirable pharmacokinetics and pharmacodynamics, etc. CS-based materials are mentioned as ideal bioactive materials for fabricating nanofibrous scaffolds. Sustained and controlled drug release and in situ gelation are other potential advantages of these scaffolds. This review highlights the latest advances in the fabrication of innovative CS-based nanofibrous scaffolds as potential bioactive materials in regenerative medicine and drug delivery systems, with an outlook on their future applications.

N2 reduction to NH3 on surfaces of Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 catalysts.

CONTEXT: The abilities of Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 as catalysts for N2-RR to create the NH3 are investigated by theoretical levels. The ∆Eadoption and ∆Eformation of Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 are investigated. The ∆Eadsorption of N2-RR intermediates and ΔGreaction of reaction steps of N2-RR on Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 are examined. In acceptable mechanisms, the *NN → *NNH step is potential limiting step and *NN → *NNH step in enzymatic mechanism is endothermic reaction. The ∆Greaction of *NHNH2 → *NH2NH2 step on Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 are -0.904, -0.928, -0.860, -0.882, -0.817 and -0.838 eV, respectively. The Co-Al18P18 and Ni-Al21N21 have the highest ∆Greaction values for reaction steps of N2-RR. Finally, it can be concluded that the Co-Al18P18, Ni-Al21N21, Fe-B24N24 and Mn-B27P2 have acceptable potential for N2-RR by acceptable pathways. METHODS: The structures of Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 and N2-RR intermediates are optimized by PW91PW91/6-311+G (2d, 2p) and M06-2X/cc-pVQZ as theoretical levels in GAMESS software. The convergence for force set displacement of Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 and N2-RR intermediates are 1.5 × 105 Hartree/Bohr and 6.0 × 10-5 Angstrom. The Opt = Tight and MaxStep = 30 are considered to optimize Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 and N2-RR intermediates. The frequencies of Co-Al18P18, Ni-Al21N21, Fe-B24N24, Mn-B27P27, Ti-C60 and Cu-Si72 and N2-RR intermediates are calculated.

Advances in electrochemical-optical dual-mode biosensors for detection of environmental pathogens.

Electrochemical techniques are commonly used to analyze and screen various environmental pathogens. When used in conjunction with other optical recognition methods, it can extend the sensing range, lower the detection limit, and offer mutual validation. Nowadays, electrochemical-optical dual-mode biosensors have ensured the accuracy of test results by integrating two signals into one, indicating their potential use in primary food safety quantitative assays and screening tests. Particularly, visible optical signals from electrochemical/colorimetric dual-mode biosensors could meet the demand for real-time screening of microbial pathogens. While electrochemical-optical dual-mode probes have been receiving increasing attention, there is limited emphasis on the design approaches for sensors intended for microbial pathogens. Here, we review the recent progress in the merging of optical and electrochemical techniques, including fluorescence, colorimetry, surface plasmon resonance (SPR), and surface enhanced Raman spectroscopy (SERS). This study particularly emphasizes the reporting of various sensing performances, including sensing principles, types, cutting-edge design approaches, and applications. Finally, some concerns and upcoming advancements in dual-mode probes are briefly outlined.

Improvement of the photoelectric dye sensitized solar cell performance using Fe/S-TiO2 nanoparticles as photoanode electrode.

A sulfur nanoparticles-incorporated iron-doped titanium oxide (Fe/TiO2) with different ratio was successfully synthesized by photolysis method and utilized as effective photoanode in dye sensitized solar cell (DSSC) application with N719 dye. The photolysis method was contained the irradiation of the Fe, S and Ti mixture solution with 15 W source irradiation, and then calcined the formed precipitate. The DSSCs fabricated with Fe/S-TiO2 photoanode appeared an improved solar-to-electrical energy conversion efficiency of 6.46, which more than pure TiO2 (3.43) below full sunlight illumination (1.5 G). The impact of Fe content on the total efficiency was also inspected and the Fe content with 6% S-TiO2 was found 5 wt%. Due to the improved the efficiency of solar cell conversion of Fe/S-TiO2 nanocomposite, it should be deemed as a potential photoanode for DSSCs with high performance.

Experimental and theoretical study of improved mesoporous titanium dioxide perovskite solar cell: The impact of modification with graphene oxide.

The present study serves experimental and theoretical analyses in developing a hybrid advanced structure as a photolysis, which is based on electrospun Graphene Oxide-titanium dioxide (GO-TiO2) nanofibers as an electron transfer material (ETMs) functionalized for perovskite solar cell (PVSCs) with GO. The prepared ETMs were utilized for the synthesis of mixed-cation (FAPbI3)0.8(MAPbBr3)0.2. The effect of GO on TiO2 and their chemical structure, electronic and morphological characteristic were investigated and discussed. The elaborated device, namely ITO/Bl-TiO2/3 wt% GO-TiO2/(FAPbI3)0.8(MAPbBr3)0.2/spiro-MeTAD/Pt, displayed 20.14% disposition and conversion solar energy with fill factor (FF) of 1.176%, short circuit current density (Jsc) of 20.56 mA/cm2 and open circuit voltage (VOC) 0.912 V. The obtained efficiency is higher than titanium oxide (18.42%) and other prepared GO-TiO2 composite nanofibers based ETMs. The developed materials and device would facilitate elaboration of advanced functional materials and devices for energy storage applications.

Effect of walnut consumption on markers of endothelial function in adults: A systematic review and meta-analysis of randomized controlled trials.

Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.

The association of exposure to polychlorinated biphenyls with lipid profile and liver enzymes in umbilical cord blood samples.

Evidence on prenatal exposure to polychlorinated biphenyls (PCBs) and its effects on newborns and potential biological mechanisms is not well defined yet. Therefore, this study aimed to examine whether PCBs are associated with lipid profile and non-invasive markers of hepatocyte injuries in samples of blood obtained from the umbilical cord. This study included 450 mothers-newborn pairs. Umbilical levels of PCBs were measured using Gas Chromatography/Mass Spectrophotometry (GC/MS). Lipid profile including low-density lipoprotein (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL-C), as well as liver enzymes i.e., alanine amino transferase (ALT), aspartate amino transferase (AST), γ-glutamyl-transferase (GGT) and alkaline phosphatase (ALP) were determined from umbilical cord blood samples. Quantile g-computation analysis was applied to evaluate the collective influence of PCBs on both lipid profiles and liver enzymes, along with the impact of lipid profiles on liver enzymes. Exposure to the mixture of PCBs was significantly associated with increases in ALP, AST, ALT, and GGT levels in cord blood samples, with increments of 90.38 U/L (95%CI: 65.08, 115.70, p < 0.01), 11.88 U/L (95%CI: 9.03, 14.74, p < 0.01), 2.19 U/L (95%CI:1.43, 2.94, p < 0.01), and 50.67 U/L (95%CI: 36.32, 65.03, p < 0.01), respectively. Additionally, combined PCBs exposure was correlated with significant increases in umbilical TG, TC, and LDL-C levels, with values of 3.97 mg/dL (95%CI: 0.86, 7.09, p = 0.01), 6.30 mg/dL (95%CI: 2.98, 9.61, p < 0.01), and 4.63 mg/dL (95%CI: 2.04, 7.23, p < 0.01) respectively. Exposure to the mixture of lipids was linked to elevated levels of AST and GGT in umbilical cord blood samples. Furthermore, a noteworthy mediating role of TC and LDL-C was observed in the association between total PCBs exposure and umbilical cord blood liver enzyme levels. Overall our findings suggested that higher levels of umbilical cord blood PCBs and lipid profile could affect liver function in newborns.

A chemometric approach based on response surface methodology for optimization of antibiotic and organic dyes removal from water samples.

In this study, the Fe3O4/rGO/Ag magnetic nanocomposite was synthesized and employed as an adsorbent for the removal of tetracycline (TC), crystal violet (CV), and methylene blue (MB) from water samples. The influential parameters in the removal process were identified and optimized using response surface methodology (RSM). Characterization of the product was performed through field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), vibrating-sample magnetometer (VSM), and X-ray diffraction (XRD) analysis. XRD and SEM analysis revealed the successful synthesis of the Fe3O4/rGO/Ag nanocomposite. EDX analysis elucidated the accuracy and clarity of the chemical composition of the magnetic nanocomposite structure. Additionally, the separation of the nano-adsorbent from the solution can be achieved using a magnetic field. Maximum removal of analytes was obtained at pH of 6, amount of nanocomposite 0.014 g, ultrasonic time of 8 min and concentration of 21 mg L-1. Under optimal conditions, the removal efficiencies for TC, CV, and MB were 91.33, 95.82, and 98.19%, respectively. Also, it was observed that after each adsorption-desorption cycle, Fe3O4/rGO/Ag magnetic nanocomposite had good stability to remove TC, CV, and MB. Achieving nearly 98% removal efficiency in optimal conditions showed that Fe3O4/rGO/Ag magnetic nanocomposite is an effective adsorbent for removing TC, CV, and MB from wastewater samples.

Amphiregulin in infectious diseases: Role, mechanism, and potential therapeutic targets.

Amphiregulin (AREG) serves as a ligand for the epidermal growth factor receptor (EGFR) and is involved in vital biological functions, including inflammatory responses, tissue regeneration, and immune system function. Upon interaction with the EGFR, AREG initiates a series of signaling cascades necessary for several physiological activities, such as metabolism, cell cycle regulation, and cellular proliferation. Recent findings have provided evidence for the substantial role of AREG in maintaining the equilibrium of homeostasis in damaged tissues and preserving epithelial cell structure in the context of viral infections affecting the lungs. The development of resistance to influenza virus infection depends on the presence of type 1 cytokine responses. Following the eradication of the pathogen, the lungs are subsequently colonized by several cell types that are linked with type 2 immune responses. These cells contribute to the process of repairing and resolving the tissue injury and inflammation caused by infections. Following influenza infection, the activation of AREG promotes the regeneration of bronchial epithelial cells, enhancing the tissue's structural integrity and increasing the survival rate of infected mice. In the same manner, mice afflicted with influenza experience rapid mortality due to a subsequent bacterial infection in the pulmonary region when both bacterial and viral infections manifest concurrently inside the same host. The involvement of AREG in bacterial infections has been demonstrated. The gene AREG experiences increased transcriptional activity inside host cells in response to bacterial infections caused by pathogens such as Escherichia coli and Neisseria gonorrhea. In addition, AREG has been extensively studied as a mitogenic stimulus in epithelial cell layers. Consequently, it is regarded as a prospective contender that might potentially contribute to the observed epithelial cell reactions in helminth infection. Consistent with this finding, mice that lack the AREG gene exhibit a delay in the eradication of the intestinal parasite Trichuris muris. The observed delay is associated with a reduction in the proliferation rate of colonic epithelial cells compared to the infected animals in the control group. The aforementioned findings indicate that AREG plays a pivotal role in facilitating the activation of defensive mechanisms inside the epithelial cells of the intestinal tissue. The precise cellular sources of AREG in this specific context have not yet been determined. However, it is evident that the increased proliferation of the epithelial cell layer in infected mice is reliant on CD4+ T cells. The significance of this finding lies in its demonstration of the crucial role played by the interaction between immunological and epithelial cells in regulating the AREG-EGFR pathway. Additional research is necessary to delve into the cellular origins and signaling mechanisms that govern the synthesis of AREG and its tissue-protective properties, independent of infection.

A graphene oxide/polyaniline nanocomposite biosensor: synthesis, characterization, and electrochemical detection of bilirubin.

The level of free bilirubin is a considerable index for the characterization of jaundice-related diseases. Herein, a biosensor was fabricated via the immobilization of bilirubin oxidase (BOx) on graphene oxide (GO) and polyaniline (PANI) that were electrochemically co-precipitated on indium tin oxide (ITO) conductive glass. The structural enzyme electrode was characterized by FTIR, XRD, and Raman spectroscopy, while the spectral and thermal properties were investigated by UV-vis and thermogravimetric analysis (TGA). Owing to the activity of the fabricated BOx/GO@PANI/ITO biosensor, it could detect free bilirubin with good selectivity and sensitivity in a low response time. The electrochemical response was studied using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). At polarization potential 0.2 V vs. Ag/AgCl, the fabricated sensor illustrated a response in only 2 s at 30 °C and pH 7.5. The LOD and LOQ for the BOx/GO@PANI/ITO biosensor were calculated and found to be 0.15 nM and 2.8 nM, respectively. The electrochemical signal showed a linear response in the concentration range 0.01-250 µM. At 5 °C, the biosensor demonstrated a half-time of 120 days, through which it could be utilized 100 times at this temperature conditions. By using a common colorimetric method, the data on bilirubin levels in serum showed a determination coefficient (R2) of 0.97.