New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.

Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system's power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract.

Evaluation of changes in exhausted T lymphocytes and miRNAs expression in the different trimesters of pregnancy in pregnant women.

BACKGROUND: Throughout the three trimesters of a typical pregnancy, we looked at changes in the expression of miRNAs and exhausted T lymphocytes for this study. METHODS AND RESULTS: Fifty healthy subjects were included in this study. The frequency of exhausted T lymphocytes was measured in isolated PBMCs using flow cytometry. PD-1, TIM-3, and related miRNAs gene expression were assessed using qRT-PCR. The analyses revealed a significant decline in PD-1 and Tim-3 expression in PBMCs from RPL women (p = 0.0003 and p = 0.001, respectively). In addition, PD-1 and TIM-3 expression increased significantly in the 2nd trimester compared with the 1st trimester of healthy pregnant women (p < 0.0001 and p = 0.0002, respectively). PD-1 and TIM-3 expression was down-regulated in the 3rd trimester compared with the 1st and 2nd trimesters. In the present study, we demonstrated that TIM-3+/CD4+, TIM-3+/CD8+, PD-1+/CD4+, and PD-1+/CD8 + exhausted T lymphocytes increased in the circulation of women in the 2nd trimester compared to the 1st and 3rd trimester. In the 3rd trimester, the expression of miR-16-5p increased significantly (p < 0.0001). miR-125a-3p expression was down and upregulated in 2nd (p < 0.0001) and 3rd (p = 0.0007) trimesters compared to 1st trimester, respectively. This study showed a significant elevation of miR-15a-5p in 3rd trimester compared to 1st trimester of pregnant women (p = 0.0002). CONCLUSIONS: Expression pattern of PD-1 and TIM3 in exhausted T lymphocytes is different not only between normal pregnant and RPL women but also in different trimesters of pregnancy. So, our results showed the role of these markers in the modulation lymphocytes activity in different stages of pregnancy.

Sirolimus- and cyclosporine-loaded nanostructured lipid carriers: Development, characterization, and in vitro evaluation in T-cell profiles of patients with a history of recurrent pregnancy loss.

Purpose: The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods: Mono-delivery and co-delivery of SRL and CsA by NLCs (S-NLCs, C-NLCs, and S-C-NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results: Well-designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co-delivery by NLCs. Following S-NLCs and C-NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17, and IL-21) and their regulators (T-bet and RORγt), as well as a lower level of an anti-inflammatory cytokine (IL-10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S-C-NLCs intervention. Conclusions: S-C-NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.

Platelet lysate and tendon healing: comparative analysis of autologous frozen-thawed PRP and ketorolac tromethamine in the treatment of patients with rotator cuff tendinopathy.

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters.

Role of miRNAs interference on ovarian functions and premature ovarian failure.

Premature ovarian failure is a to some extent unknown and intricate problem with diverse causes and clinical manifestations. The lack of ovarian sex hormones presumably is effective in the occurrence of ovarian failure. Our progress in this field has been very little despite undertaken scientific research endeavors; scholars still are trying to understand the explanation of this dilemmatic medical condition. In contrast, the practice of clinical medicine has made meaningful strides in providing assurance to the women with premature ovarian insufficiency that their quality of life as well as long-term health can be optimized through timely intervention. Very recently Scientists have investigated the regulating effects of small RNA molecules on steroidogenesis apoptosis, ovulation, gonadal, and corpus luteum development of ovaries. In this literature review, we tried to talk over the mechanisms of miRNAs in regulating gene expression after transcription in the ovary. Video abstract.

TIGIT and CD155 as Immune-Modulator Receptor and Ligand on CD4+ T cells in Preeclampsia Patients.

One of the main characteristics of preeclampsia (PE) is systemic inflammation. CD4+ FoxP3+ cells play a critical role in both fetomaternal tolerance and successful pregnancy. T-cell immunoglobulin, as well as immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT)/CD155 pathway, possesses critical parts in the development of normal pregnancy by promoting regulatory T (Treg) cells. However, in PE, the relationship between TIGIT/CD155 and Treg differentiation has not been entirely clarified. In the current report, we aimed to assess the frequency of TIGIT and CD155 expressing TCD4+ cells in both PE and healthy pregnant women, as well as evaluating the amount of inflammatory and inhibitory cytokines at both mRNA and protein levels before and after blocking TIGIT and CD155. In the present report, 59 healthy, and 52 PE patients were designated to obtain their venous blood. The isolation of peripheral blood mononuclear cells (PBMCs) was performed from the blood samples, and PBMCs were then cultured in the RPMI1640 medium. The percentage of CD155+ and TIGIT+ CD4+ cells was assessed by flow cytometry in PBMCs. Cell culture supernatants were utilized to evaluate the secretory levels of transforming growth factor beta (TGF-ß), interleukin (IL)-10, IL-17, tumor necrosis factor alpha (TNF-α), and IL-1 ß, using enzyme-linked immunosorbent assay technique in pregnant women with or without PE both before and after blocking TIGIT and CD155. The mRNA expression of Foxp3, TIGIT, CD155, SHP-1, TGF-ß, IL-10, IL-17, TNF-α, and IL-1ß was also assessed by qRT-PCR in PBMCs before and after blocking TIGIT and CD155 in both populations. The data showed a significant decrease in the frequency of TIGIT+ CD4+ and CD155+ CD4+ T cells in PE women, compared to the control group. Our results showed decreased protein and mRNA levels of TIGIT, CD155, IL-10, FOXP3, and SHP-1 in PE patients. In addition, significant improvements in the levels of IL-17, TNF-α, and IL-1ß were observed in PE patients, as compared with the controls. However, blocking TIGIT and CD155 could increase these inflammatory cytokines and decrease anti-inflammatory cytokines. The data obtained in this report illustrated that there existed an imbalance between inflammatory and anti-inflammatory profiles, with an inflammatory status polarization, in PE patients. Additionally, TIGIT/CD155 showed a positive effect on immune regulation by activating ITIM, demonstrating the potential therapeutic value of the TIGIT/CD155 pathway in PE treatment. Also, using some proteins or materials that increased TIGIT/CD155 pathways activity and can be a therapeutic approach in PE.

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. METHODS: Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR-27, miR-17, and miR-146a) and cytokines including Interleukin-10 (IL-10), TGF-ß, and IL-6 were assessed by real-time polymerase chain reaction. Furthermore, enzyme-linked immunosorbent assay was done to determine the secretion levels of cytokines. RESULTS: After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT-PCR data indicated that the expression of miR-17 and miR-27 were significantly decreased following nanocurcumin treatment while miR-146a and FoxP3 were significantly increased. Moreover, nanocurcumin-treated group had high levels of IL-10 and TGF-ß and low levels of IL-6 production than control group. CONCLUSION: The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

Immunological and oxidative stress biomarkers in Ankylosing Spondylitis patients with or without metabolic syndrome.

Ankylosing Spondylitis (AS) is a chronic inflammatory disorder of the spine and sacroiliac joints with unidentified etiology closely associated with metabolic syndrome (MetS). Recent studies have reported that immunological and oxidative stress factors are implicated in AS pathogenesis. The aim of this study was to investigate the oxidative and immunological factors in AS patients with or without MetS compare to control group. Real-Time PCR measured expression level of cytokines, transcription factors and related miRNAs. In addition, Th17 and Treg frequencies and cytokines secretion were evaluated by flowcytometry and ELISA methods, respectively. The oxidative stress biomarkers were also assessed with biochemical methods. In AS patients with MetS, higher Th17 and lower Treg frequency were observed. Increased levels of NF-kB and AP-1 mRNA expression were seen in AS patients with MetS (p = 0.0263 and p = 0.0104, respectively). MiR-146a and miR-223 were significantly decreased (p = 0.0005, p = 0.0161, respectively) and increase in miR-21 (p = 0.0002) was observed in AS patients with MetS compared to AS patients without MetS. Additionally, the secretion of TNF-α (p = 0.0167), IL-1ß (p = 0.303), CCL2 (p = 0.0254), CCL3 (p = 0.0119), CXCL8 (p = 0.0364), adiponectin (p = 0.0183) and the levels of SOD (p = 0.0421), NO (p = 0.0451) and CAT (p = 0.0128) were increased in AS patients with MetS. We were not observed significant differences in TOS and GPX levels between studied groups. The higher levels of oxidative stress and immunological inflammatory markers in AS patients with MetS provide further evidences on the oxidative stress and immunological relationship in these patients.

Cyclosporine A improves pregnancy outcomes in women with recurrent pregnancy loss and elevated Th1/Th2 ratio.

Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)-dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real-time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme-linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T-bet mRNA expression (p < 0.0001), interferon-γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine-treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.

Cytokine profile, Treg/Th17 cell frequency changes during different posttransplantational time points in patients undergoing renal transplantation.

Renal transplantation is the best therapeutic approach for end stage renal dysfunction patients. There are direct relationships between proportions of Treg cells, Treg/Th17 cells ratio and secreted immunosuppressive cytokines with increased survival rate of the transplanted organ. The aim of this study was the measurement of Treg and Th17 cells frequency and their secreted cytokines. Ninety renal-transplanted patients were divided in three groups based on times after transplantation (1-6 month, 6-36 month, and more than 3 years). Treg and Th17 cells frequency, expression level of their transcription factors and cytokines, and their secreted cytokines level were measured in these groups. Higher expression level of Interleukin (IL)-10 and FoxP3 mRNA were observed in patients who had longer posttransplantation time. In contrast, lower mRNA expressions of IL-6, IL-17, IL-23, and TGF-ß were observed in this group. Receptor γt showed no significant changes in studied groups. In addition IL-10 level was increased and IL-6, IL-17, IL-23, and TGF-ß level were decreased in patients who had longer posttransplantation time. Treg cells frequency was raised in mentioned group whereas no remarkable changes were observed in Th17 cell frequency. The present study declared that in stable renal transplantation, over time, the percentage of Treg cells and Treg/Th17 ration is increased. This increase in ratio induces a change in cytokine profile, resulting in an increased immunosuppressive cytokines such as IL-10 leading to increase in the survival rate of the transplanted organ.

Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function.

Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety-four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty-four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre- and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.

Nanocurcumin: A novel strategy in treating ankylosing spondylitis by modulating Th17 cells frequency and function.

Ankylosing spondylitis (AS) is a chronic rheumatic disease which mainly affects the axial skeleton and sacroiliac joints. T-helper 17 (Th17) cells have been reportedly involved in AS pathogenesis. Nanocurcumin is considered to be beneficial, as an anti-inflammatory compound, in AS patients treatment. In this study, Th17-related immunological parameters were evaluated in AS patients. Transcription factors messenger RNA (mRNA) expression level, cytokines, and related microRNAs (miRNAs) were measured by real-time polymerase chain reaction. Additionally, Th17 frequency and cytokines secretion were evaluated by flow cytometry and enzyme-linked immunosorbent assay tests, respectively. The frequency of Th17 was higher in AS patients. Gained data from nanocurcumin group also demonstrated that retinoic acid-related orphan receptor γ (RORγt) and interleukin-17 (IL-17) mRNA expression levels were significantly decreased (P = 0.0001 and 0.0006, respectively), as the decrease also happened in Th17-associated miRNAs including miR-141, miR-155, and miR-200 ( P = 0.04, P = 0.02, and P < 0.0001, respectively). Posttreatment data of miR-155 and miR-200 in the nanocurcumin and placebo groups also showed a higher expression level in the placebo group compared with nanocurcumin-treated patients. Some clinical symptoms of AS patients were also improved at the end of the treatment process. The results of this study showed the potential ability of nanocurcumin to regulate Th17 cells activity in AS patients. This study provided further evidence on the function and underlying mechanism of nanocurcumin helping better treatment of AS.

Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options.

Small extracellular vesicles called exosomes play a crucial part in promoting intercellular communication. They act as intermediaries for the exchange of bioactive chemicals between cells, released into the extracellular milieu by a variety of cell types. Within the context of cancer progression, metastasis is a complex process that plays a significant role in the spread of malignant cells from their main site of origin to distant anatomical locations. This complex process plays a key role in the domain of cancer-related deaths. In summary, the trajectory of current research in the field of exosome-mediated metastasis is characterized by its unrelenting quest for more profound understanding of the molecular nuances, the development of innovative diagnostic tools and therapeutic approaches, and the unwavering dedication to transforming these discoveries into revolutionary clinical applications. This unrelenting pursuit represents a shared desire to improve the prognosis for individuals suffering from metastatic cancer and to nudge the treatment paradigm in the direction of more effective and customized interventions.

Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside.

A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors.

Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

Analysis of Th17 cell population and expression of microRNA and factors related to Th17 in patients with premature ovarian failure.

Folliculogenesis is the process where follicles in the ovaries develop and eventually lead to ovulation. Any disruption to this process can cause premature ovarian failure. miR-326 is one of the microRNAs whose expression leads to Th17 production. Th17 activates the immune system to respond more vigorously, and by producing interlukins and cytokines causes inflammation and autoimmune disorders. Th17-induced inflammation and Th17/Treg imbalance can result in POF. This investigation took samples from 30 POF patients and 30 healthy people. The study utilized PCR to assess the expression levels of cytokines, specific transcription factor (ROR-γt), and miR-326. Additionally, ELISA was employed to analyze serum levels of IL-17, IL-21, IL-23. Furthermore, flow cytometry was utilized to determine the frequency of Th17. Compared to the control group, our results demonstrated a rise in the transcription factor RORɣt and a considerable rise in the frequency of Th17 cells in patients with POF. The level of inflammatory cytokines IL-17, IL-21, and IL-23 secreted in serum samples of patients with POF increased significantly compared to the control group. Results of investigating microRNA associated with Th17 cells also showed increased expression of miR-326 in females suffering from POF. The elevation of pro-inflammatory markers in women with POF contrary to the control group underscores the significant involvement of the immune system in pregnancy disorders pathogenesis. Consequently, immunological factors may serve as promising biomarkers for predicting POF likelihood in high-risk women in the future.

New immunotherapeutic approaches for cancer treatment.

Neoplasms are a worldwide recognized non-contagious disease which has the most mortality rate after cardiovascular diseases. For decades, there has been a vast amount of study on treatment methods of cancer which has led to conventional therapies such as chemotherapy, radiation therapy, surgery and so on. Clinicians and researchers believed that there is an urgent need, considering the high rate of incidence and prevalence, for an alternative treatment option which is more efficacious and has less adverse effects than the above-mentioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and became one of the fastest developing therapeutic approaches. Different kinds of immunotherapies are FDA approved and available for treatment of various cancer types. In this review, we have summarized the major immunotherapy methods including checkpoint inhibitors, CAR T cell therapies and cancer vaccines. Furthermore, application of combination therapy, precision medicine, biomarker discovery, overcoming resistance and reduction of adverse effects are discussed in this study.

Application of Pt@ZIF-8 nanocomposite-based electrochemical biosensor for sensitive diagnosis of tau protein in Alzheimer's disease patients.

Alzheimer's disease (AD) is a progressive brain disorder characterized by the ongoing decline of brain functions. Studies have revealed the detrimental effects of hyperphosphorylated tau (p-tau) protein fibrils in AD pathogenesis, highlighting the importance of this factor in the early-stage detection of AD conditions. We designed an electrochemical immunosensor for quantitative detection of the cis conformation of the p-tau protein (cis-p-tau) employing platinum nanoparticles (Pt NPs) supported on zeolitic imidazolate frameworks (ZIF) for modifying the glassy carbon electrode (GCE) surface. Under optimum conditions, the immunosensor selectively and sensitively detected cis-p-tau within the broad linear range of 1 fg mL-1 to 10 ng mL-1 and the low limit of detection (LOD) of 1 fg mL-1 with desired reproducibility and stability. Furthermore, the fabricated immunosensor's performance was examined for the cis-p-tau analysis in the serum of AD patients, indicating its accuracy and feasibility for real-sample analysis. Notably, this is the first application of Pt@ZIF-8 nanocomposite in fabricating a valid immunosensor for selective cis-p-tau detection, even in the presence of trans-p-tau. It is worth mentioning that the enzyme-linked immunosorbent assay (ELISA) reference technique is not able to evaluate pico- or femtomolar concentrations of cis-p-tau, making the fabricated immunosensor superior for early-stage measurement and screening of AD.

An updated review of a novel method for examining P53 mutations in different forms of cancer.

In the past fifteen years, it has been clear that tumor-associated p53 mutations can cause behaviors distinct from those brought on by a simple loss of p53's tumor-suppressive function in its wild-type form. Many of these mutant p53 proteins develop oncogenic characteristics that allow them to encourage cell survival, invasion, and metastasis. But it is now understood that the immune response is also significantly influenced by the cancer cell's p53 status. The recruitment and activity of myeloid and T cells can be impacted by p53 loss or mutation in malignancies, allowing immune evasion and accelerating cancer growth. Additionally, p53 can work in immune cells, which can have various effects that either hinder or assist the growth of tumors. In this review article, we examined different mutations of P53 in some significant cancers, such as liver, colorectal, and prostate, and reviewed some new therapeutic approaches.

Dysregulation of P53 in breast cancer: Causative factors and treatment strategies.

One of the most prevalent cancers impacting women worldwide is breast cancer. Although there are several risk factors for breast cancer, the p53 gene's function has recently received much attention. The "gatekeeper" gene, or p53, is sometimes referred to as such since it is crucial in controlling cell proliferation and preventing the development of malignant cells. By identifying DNA damage and initiating cellular repair processes, p53 usually functions as a tumor-suppressor. But p53 gene alterations can result in a lack of function, allowing cells to divide out of control and perhaps triggering the onset of cancer. Various factors, such as mutation genes, signaling pathways, and hormones, can dysregulate P53 proteins and cause breast cancer. A promising strategy for individualized cancer treatment involves focusing on p53 mutations in breast cancer. While numerous techniques, including gene therapy and small compounds, have shown promise, further study is required to create safe and efficient treatments to target p53 mutations in breast cancer successfully.