Label-Free Field Effect Transistors (FETs) for Fabrication of Point-of-Care (POC) Biomedical Detection Probes.

Field effect transistors (FETs)-based detection probes are powerful platforms for quantification in biological media due to their sensitivity, ease of miniaturization, and ability to function in biological media. Especially, FET-based platforms have been utilized as promising probes for label-free detections with the potential for use in real-time monitoring. The integration of new materials in the FET-based probe enhances the analytical performance of the developed probes by increasing the active surface area, rejecting interfering agents, and providing the possibility for surface modification. Furthermore, the use of new materials eliminates the need for traditional labeling techniques, providing rapid and cost-effective detection of biological analytes. This review discusses the application of materials in the development of FET-based label-free systems for point-of-care (POC) analysis of different biomedical analytes from 2018 to 2024. The mechanism of action of the reported probes is discussed, as well as their pros and cons were also investigated. Also, the possible challenges and potential for the fabrication of commercial devices or methods for use in clinics were discussed.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Incorporation of immunotherapies and nanomedicine to better normalize angiogenesis-based cancer treatment.

Neoadjuvant targeting of tumor angiogenesis has been developed and approved for the treatment of malignant tumors. However, vascular disruption leads to tumor hypoxia, which exacerbates the treatment process and causes drug resistance. In addition, successful delivery of therapeutic agents and efficacy of radiotherapy require normal vascular networks and sufficient oxygen, which complete tumor vasculopathy hinders their efficacy. In view of this controversy, an optimal dose of FDA-approved anti-angiogenic agents and combination with other therapies, such as immunotherapy and the use of nanocarrier-mediated targeted therapy, could improve therapeutic regimens, reduce the need for administration of high doses of chemotherapeutic agents and subsequently reduce side effects. Here, we review the mechanism of anti-angiogenic agents, highlight the challenges of existing therapies, and present how the combination of immunotherapies and nanomedicine could improve angiogenesis-based tumor treatment.

Virological Suppression and its Predictors Among HIV/AIDS Patients on Antiretroviral Therapy in Ethiopia: Systematic Review and Meta-analysis.

Background: Achieving viral load suppression is crucial for the prevention of complications and deaths related to HIV infection. Ethiopia has embraced the worldwide 95-95-95 target, but there is no national representative information regarding virological suppression. Therefore, this review aims to determine the pooled virological suppression rate and identify the pooled effect of contributing factors of viral suppression for HIV-positive patients on antiretroviral therapy in Ethiopia. Methods: We systematically searched websites and databases, including online repositories, to obtain primary studies. Two reviewers assessed the quality of the included articles using the Newcastle-Ottawa Scale appraisal checklist. Publication bias was checked using Egger's regression test, the heterogeneity of the studies was assessed using I2 statistics and Q statistics, and a sensitivity analysis was performed to identify any outlier results in the included studies. The Der Simonian Laird random-effects model was used to estimate the overall proportion of viral suppression, and STATA 17 statistical software was used for all types of analysis. Results: A total of 21 eligible articles primarily conducted in Ethiopia using HIV program data were used for this quantitative synthesis. The overall pooled virological suppression rate was 71% (95% CI, 64%-77%). The pooled effects of poor adherence to ART (adjusted odds ratio [AOR], 0.33; 95% CI, 0.28-0.40), body mass index (18.5-24.9 kg/m2; AOR, 1.8; 95% CI, 1.37-2.36), disclosure (AOR, 1.41; 95% CI, 1.05-1.89), absence of opportunistic infection (AOR, 1.68; 95% CI, 1.43-1.97), and high baseline viral load count (AOR, 0.65; 95% CI, 0.52-0.81) were identified as significant predictors of viral suppression. Conclusions: The overall pooled percentage of virological suppression was low compared with the global target of viral suppression and the Ethiopian Public Health Institute report. Poor adherence, normal body mass index, disclosure, absence of opportunistic infection, and high baseline viral load count were factors contributing to viral suppression in Ethiopia. Responsible stakeholders should maximize their efforts to achieve the global target of virological suppression by addressing significant predictors.

The mechanisms behind the dual role of long non-coding RNA (lncRNA) metastasis suppressor-1 in human tumors: Shedding light on the molecular mechanisms.

When the expression levels of metastasis suppressor-1 (MTSS1) were discovered to be downregulated in a metastatic cancer cell line in 2002, it was proposed that MTSS1 functioned as a suppressor of metastasis. The 755 amino acid long protein MTSS1 connects to actin and organizes the cytoskeleton. Its gene is located on human chromosome 8q24. The suppressor of metastasis in metastatic cancer was first found to be MTSS1. Subsequent reports revealed that MTSS1 is linked to the prevention of metastasis in a variety of cancer types, including hematopoietic cancers like diffuse large B cell lymphoma and esophageal, pancreatic, and stomach cancers. Remarkably, conflicting results have also been documented. For instance, it has been reported that MTSS1 expression levels are elevated in a subset of melanomas, hepatocellular carcinoma associated with hepatitis B, head and neck squamous cell carcinoma, and lung squamous cell carcinoma. This article provides an overview of the pathological effects of lncRNA MTSS1 dysregulation in cancer. In order to facilitate the development of MTSS1-based therapeutic targeting, we also shed light on the current understanding of MTS1.

The interaction between lncRNAs and transcription factors regulating autophagy in human cancers: A comprehensive and therapeutical survey.

Autophagy, as a highly conserved cellular process, participates in cellular homeostasis by degradation and recycling of damaged organelles and proteins. Besides, autophagy has been evidenced to play a dual role through cancer initiation and progression. In the early stage, it may have a tumor-suppressive function through inducing apoptosis and removing damaged cells and organelles. However, late stages promote tumor progression by maintaining stemness features and induction of chemoresistance. Therefore, identifying and targeting molecular mechanisms involved in autophagy is a potential therapeutic strategy for human cancers. Multiple transcription factors (TFs) are involved in the regulation of autophagy by modulating the expression of autophagy-related genes (ATGs). In addition, a wide array of long noncoding RNAs (lncRNAs), a group of regulatory ncRNAs, have been evidenced to regulate the function of these autophagy-related TFs through tumorigenesis. Subsequently, the lncRNAs/TFs/ATGs axis shows great potential as a therapeutic target for human cancers. Therefore, this review aimed to summarize new findings about the role of lncRNAs in regulating autophagy-related TFs with therapeutic perspectives.

A review of recent advancement in covalent organic framework (COFs) synthesis and characterization with a focus on their applications in antibacterial activity.

The primary objective of this review is to present a comprehensive examination of the synthesis, characterization, and antibacterial applications of covalent organic frameworks (COFs). COFs represent a distinct category of porous materials characterized by a blend of advantageous features, including customizable pore dimensions, substantial surface area, and adaptable chemical properties. These attributes position COFs as promising contenders for various applications, notably in the realm of antibacterial activity. COFs exhibit considerable potential in the domain of antibacterial applications, owing to their amenability to functionalization with antibacterial agents. The scientific community is actively exploring COFs that have been imbued with metal ions, such as copper or silver, given their observed robust antibacterial properties. These investigations strongly suggest that COFs could be harnessed effectively as potent antibacterial agents across a diverse array of applications. Finally, COFs hold immense promise as a novel class of materials for antibacterial applications, shedding light on the synthesis, characterization, and functionalization of COFs tailored for specific purposes. The potential of COFs as effective antibacterial agents beckons further exploration and underscores their potential to revolutionize antibacterial strategies in various domains.

Exploring the Therapeutic Potential of Lawsone and Nanoparticles in Cancer and Infectious Disease Management.

Lawsone, a naturally occurring compound found in henna, has been used in traditional medicine for centuries due to its diverse biological activities. In recent years, its nanoparticle-based structure has gained attention in cancer and infectious disease research. This review explores the therapeutic potential of lawsone and its nanoparticles in the context of cancer and infectious diseases. Lawsone exhibits promising anticancer properties by inducing apoptosis and inhibiting cell proliferation, while its nanoparticle formulations enhance targeted delivery and efficacy. Moreover, lawsone demonstrates significant antimicrobial effects against various pathogens. The unique physicochemical properties of lawsone nanoparticles enable efficient cellular uptake and targeted delivery. Potential applications in combination therapy and personalized medicine open new avenues for cancer and infectious disease treatment. While clinical trials are needed to validate their safety and efficacy, lawsone-based nanoparticles offer hope in addressing unmet medical needs and revolutionizing therapeutic approaches.

Magnetic nanocomposite based on chitosan-gelatin hydrogel embedded with copper oxide nanoparticles: A novel and promising catalyst for the synthesis of polyhydroquinoline derivatives.

Nanocatalysts are vital in several domains, such as chemical processes, energy generation, energy preservation, and environmental pollution mitigation. An experimental study was conducted at room temperature to evaluate the catalytic activity of the new gelatin-chitosan hydrogel/CuO/Fe3O4 nanocomposite in the asymmetric Hantzsch reaction. All components of the nanocomposite exhibit a synergistic effect as a Lewis acid, promote the reaction. Dimedone, ammonium acetate, ethyl acetoacetate, and other substituted aldehydes were used to synthesize diverse polyhydroquinoline derivatives. The nanocomposite exhibited exceptional efficacy (over 90 %) and durability (retaining 80 % of its original capacity after 5 cycles) as a catalyst in the one-pot asymmetric synthesis of polyhydroquinoline derivatives. Also, turnover numbers (TON) and turnover frequency (TOF) have been checked for catalyst (TON and TOF = 50,261 and 100,524 h-1) and products. The experiment demonstrated several benefits, such as exceptional product efficacy, rapid reaction time, functioning at ambient temperature without specific requirements, and effortless separation by the use of an external magnet after the reaction is finished. The results suggest the development of a magnetic nanocatalyst with exceptional performance. The composition of the Ge-CS hydrogel/CuO/Fe3O4 nanocomposite was thoroughly analyzed using several methods including FT-IR, XRD, FE-SEM, EDX, VSM, BET, and TGA. These analyses yielded useful information into the composition and characteristics of the nanocomposite, hence further enhancing the knowledge of its possible uses.

Isothermal amplification methods in cancer-related miRNA detection; a new paradigm in study of cancer pathology.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression. They are involved in a wide range of biological processes, including development, differentiation, cell cycle regulation, and response to stress. Numerous studies have demonstrated that miRNAs are present in different bodily fluids, which could serve as an important biomarker. The advancement of techniques and strategies for the identification of cancer-associated miRNAs in human specimens offers a novel opportunity to diagnose cancer in early stages, predict patient prognosis and evaluate response to treatment. Isothermal techniques including loop-mediated isothermal amplification (LAMP), rolling circle amplification (RCA), or recombinase polymerase amplification (RPA) offer simplicity, efficiency, and rapidity in miRNA detection processes. In contrast to traditional PCR (polymerase chain reaction), these techniques analysis and quantify miRNA molecules in specimens using a single constant temperature. In this comprehensive review, we summarized the recent advances in cancer-related miRNA detection via highly sensitive isothermal amplification methods by more focusing on the involved mechanism.

Aptamer-Magnetic Nanoparticle Complexes for Powerful Biosensing: A Comprehensive Review.

The selective and sensitive diagnosis of diseases is a significant matter in the early stages of the cure of illnesses. To elaborate, although several types of probes have been broadly applied in clinics, magnetic nanomaterials-aptamers, as new-generation probes, are becoming more and more attractive. The presence of magnetic nanomaterials brings about quantification, purification, and quantitative analysis of biomedical, especially in complex samples. Elaborately, the superparamagnetic properties and numerous functionalized groups of magnetic nanomaterials are considered two main matters for providing separation ability and immobilization substrate, respectively. In addition, the selectivity and stability of aptamer can present a high potential recognition element. Importantly, the integration of aptamer and magnetic nanomaterials benefits can boost the performance of biosensors for biomedical analysis by introducing efficient and compact probes that need low patient samples and fast diagnosis, user-friendly application, and high repeatability in the quantification of biomolecules. The primary aim of this review is to suggest a summary of the effect of the employed other types of nanomaterials in the fabrication of novel aptasensors-based magnetic nanomaterials and to carefully explore various applications of these probes in the quantification of bioagents. Furthermore, the application of these versatile and high-potential probes in terms of the detection of cancer cells and biomarkers, proteins, drugs, bacteria, and nucleoside were discussed. Besides, research gaps and restrictions in the field of biomedical analysis by magnetic nanomaterials-aptamers will be discussed.

Microfluidic-based nanoemulsion of Ocimum basilicum extract: Constituents, stability, characterization, and potential biomedical applications for improved antimicrobial and anticancer properties.

This paper reports on the findings from a study that aimed to identify and characterize the constituents of Ocimum basilicum extract using gas chromatography-mass spectrometry (GC-MS) analysis, as well as assess the physicochemical properties and stability of nanoemulsions formulated with O. basilicum extract. The GC-MS analysis revealed that the O. basilicum extract contained 22 components, with Caryophyllene and Naringenin identified as the primary active constituents. The nanoemulsion formulation demonstrated excellent potential for use in the biomedical field, with a small and uniform particle size distribution, a negative zeta potential, and high encapsulation efficiency for the O. basilicum extract. The nanoemulsions exhibited spherical morphology and remained physically stable for up to 6 months. In vitro release studies indicated sustained release of the extract from the nanoemulsion formulation compared to the free extract solution. Furthermore, the developed nanoformulation exhibited enhanced anticancer properties against K562 cells while demonstrating low toxicity in normal cells (HEK293). The O. basilicum extract demonstrated antimicrobial activity against Pseudomonas aeruginosa, Candida albicans, and Staphylococcus epidermidis, with a potential synergistic effect observed when combined with the nanoemulsion. These findings contribute to the understanding of the constituents and potential applications of O. basilicum extract and its nanoemulsion formulation in various fields, including healthcare and pharmaceutical industries. Further optimization and research are necessary to maximize the efficacy and antimicrobial activity of the extract and its nanoformulation. RESEARCH HIGHLIGHTS: This study characterized the constituents of O. basilicum extract and assessed the physicochemical properties and stability of its nanoemulsion formulation. The O. basilicum extract contained 22 components, with Caryophyllene and Naringenin identified as the primary active constituents. The nanoemulsion formulation demonstrated excellent potential for biomedical applications, with sustained release of the extract, low toxicity, and enhanced anticancer and antimicrobial properties. The findings contribute to the understanding of the potential applications of O. basilicum extract and its nanoemulsion formulation in healthcare and pharmaceutical industries, highlighting the need for further optimization and research.

Artificial intelligence in cancer diagnosis: Opportunities and challenges.

Since cancer is one of the world's top causes of death, early diagnosis is critical to improving patient outcomes. Artificial intelligence (AI) has become a viable technique for cancer diagnosis by using machine learning algorithms to examine large volumes of data for accurate and efficient diagnosis. AI has the potential to alter the way cancer is detected fundamentally. Still, it has several disadvantages, such as requiring a large amount of data, technological limitations, and ethical concerns. This overview looks at the possibilities and restrictions of AI in cancer detection, as well as current applications and possible future developments. We can better understand how to use AI to improve patient outcomes and reduce cancer mortality rates by looking at its potential for cancer detection.

The cardioprotective effects of cerium oxide nanoparticles against the poisoning generated by aluminum phosphide pesticide: Controlling oxidative stress and mitochondrial damage.

BACKGROUND: Aluminum phosphide (AlP) is a well-known toxic compound used as an agricultural pesticide to prevent insect damage to stored crops. However, even if just a small amount was consumed, it caused lasting harm to the human body and, in acute concentrations, death. The current study employed cerium oxide nanoparticles (CeO2 NPs) to reduce oxidative stress and various harmful outcomes of AlP poisoning. METHODS: Following finding effective concentrations of CeO2 NPs via MTT assay, Human Cardiac Myocyte (HCM) cells were pre-treated with CeO2 NPs for 24 h. After that, they were exposed to 2.36 µM AlP. The activity of oxidative stress and mitochondrial biomarkers, including mitochondrial swelling, mitochondrial membrane potential, and cytochrome c release, were evaluated in HCM cells. Finally, the population of apoptotic and necrotic cells was assessed via flow cytometry. RESULTS: After 24 h, data revealed that all tested concentrations of CeO2 NPs were safe, and 25 and 50 µM of that were selected as effective concentrations. Oxidative stress markers (malondialdehyde, protein carbonyl, superoxide dismutase, and catalase) showed that CeO2 NPs could successfully decrease AlP poisoning due to their antioxidant characteristics. Mitochondrial markers were also recovered by pre-treatment of HCM cells with CeO2 NPs. Furthermore, pre-treating with CeO2 NPs could compensate for the reduction of live cells with AlP and cause a diminishing in the population of early and late apoptotic cells. CONCLUSION: As a result, it is evident that CeO2 NPs, through the recovery of oxidative stress and mitochondrial damages caused by AlP, reduce apoptosis and have therapeutic potentials on HCM cells.

Unveiling innovative therapeutic strategies and future trajectories on stimuli-responsive drug delivery systems for targeted treatment of breast carcinoma.

This comprehensive review delineates the latest advancements in stimuli-responsive drug delivery systems engineered for the targeted treatment of breast carcinoma. The manuscript commences by introducing mammary carcinoma and the current therapeutic methodologies, underscoring the urgency for innovative therapeutic strategies. Subsequently, it elucidates the logic behind the employment of stimuli-responsive drug delivery systems, which promise targeted drug administration and the minimization of adverse reactions. The review proffers an in-depth analysis of diverse types of stimuli-responsive systems, including thermoresponsive, pH-responsive, and enzyme-responsive nanocarriers. The paramount importance of material choice, biocompatibility, and drug loading strategies in the design of these systems is accentuated. The review explores characterization methodologies for stimuli-responsive nanocarriers and probes preclinical evaluations of their efficacy, toxicity, pharmacokinetics, and biodistribution in mammary carcinoma models. Clinical applications of stimuli-responsive systems, ongoing clinical trials, the potential of combination therapies, and the utility of multifunctional nanocarriers for the co-delivery of assorted drugs and therapies are also discussed. The manuscript addresses the persistent challenge of drug resistance in mammary carcinoma and the potential of stimuli-responsive systems in surmounting it. Regulatory and safety considerations, including FDA guidelines and biocompatibility assessments, are outlined. The review concludes by spotlighting future trajectories and emergent technologies in stimuli-responsive drug delivery, focusing on pioneering approaches, advancements in nanotechnology, and personalized medicine considerations. This review aims to serve as a valuable compendium for researchers and clinicians interested in the development of efficacious and safe stimuli-responsive drug delivery systems for the treatment of breast carcinoma.

Exosomes derived from adipose stem cells in combination with hyaluronic acid promote diabetic wound healing.

Diabetic wound is one of the main challenges in dermatology. Although stem cell-based treatment has therapeutic benefits in wound repair, the clinical application is still limited. Herein we investigated whether adipose stem cells -derived exosomes (Exo) loaded on hyaluronic acid (HA) could promote healing in diabetic rats. Sixty diabetic rats were randomly planned into the control group, Exo group, HA group, and HA+Exo group. On days 7, 14, and 21, five rats from each group were sampled for stereological, molecular, and tensiometrical assessments. Our results indicated that the wound closure rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts, the length density blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were significantly higher in the treated groups than in the control group, and these changes were more obvious in the HA+Exo ones. Furthermore, the expression of TGF-ß and VEGF genes were meaningfully upregulated in all treated groups compared to the control group and were greater in the HA+Exo group. This is while expression of TNF-α and IL-1ß, as well as numerical densities of neutrophils decreased more considerably in the HA+Exo group in comparison to the other groups. Generally, it was found that using both HA injection and exosomes has more effect on diabetic wound healing.

LncRNA-miRNA interaction is involved in colorectal cancer pathogenesis by modulating diverse signaling pathways.

LncRNAs function as molecular sponges for miRNAs to control their availability for targeting mRNA molecules. This procedure indirectly regulates the expression of cancer-related genes. Some lncRNAs also directly interact with miRNAs, leading to their degradation or sequestration, which can negatively impact gene expression. miRNAs, on the other hand, play a critical role in controlling the expression of genes, including oncogenes and tumor suppressor genes. Multiple types of cancer have been linked to the onset and progression of miRNA dysregulation. Even though there is a lot of potential for treating CRC by targeting the LncRNA-miRNA axis, several challenges remain to be overcome. The specificity of the targeting approach, delivery methods, resistance, safety, and cost-effectiveness are critical research areas that must be addressed to advance this field and improve treatment outcomes for people with CRC.

An efficient magnetic nanoadsorbent based on functionalized graphene oxide with gellan gum hydrogel embedded with MnFe layered double hydroxide for adsorption of Indigo carmine from water.

The primary objective of this investigation was to synthesize a novel antibacterial nanocomposite consisting of natural gellan gum (GG) hydrogel, MnFe LDH, GO, and Fe3O4 nanoparticle, which was developed to adsorb Indigo carmine (IC). The GG hydrogel/MnFe LDH/GO/Fe3O4 nanocomposite was characterized through different analytical, microscopic, and biological methods. The results of adsorption experiments reveal that 0.004 g of the nanocomposite can remove 98.38 % of IC from a solution with an initial concentration of 100 mg/L, within 1 h at room temperature and under acidic pH conditions. Moreover, the nanocomposite material effectively suppressed the in vitro growth of both E. coli and S. aureus strains, with inhibitory rates of 62.33 % and 53.82 %, respectively. The isotherm data obtained in this investigation were fitted by linear and non-linear forms of Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) isotherms equations. The results of the adsorption kinetics study indicated that the pseudo-second-order model best described the experimental data. The findings of this study suggest that the synthesized nanocomposites hold great potential as effective adsorbents for removing IC and bacteria from aqueous solutions.

A comprehension of signaling pathways and drug resistance; an insight into the correlation between microRNAs and cancer.

Despite the development of numerous therapies, cancer remains an incurable disease due to various factors, including drug resistance produced by cancer cells. MicroRNAs (miRNAs) regulate different target genes involved in biological and pathological processes, including cancer, through post-transcriptional mechanisms. The development of drug resistance in cancer treatment is a significant barrier because it decreases drug uptake, cellular transport, and changes in proteins involved in cell proliferation, survival, and apoptotic pathways. Numerous studies have found a connection between miRNAs and the development of drug resistance in cancer cells. This paper provides a broad overview of how miRNAs regulate signaling pathways and influence treatment resistance in different cancers.

Involving stemness factors to improve CAR T-cell-based cancer immunotherapy.

Treatment with chimeric antigen receptor (CAR) T cells indicated remarkable clinical responses with liquid cancers such as hematological malignancies; however, their therapeutic efficacy faced with many challenges in solid tumors due to severe toxicities, antigen evasion, restricted and limited tumor tissue trafficking and infiltration, and, more importantly, immunosuppressive tumor microenvironment (TME) factors that impair the CAR T-cell function adds support survival of cancer stem cells (CSCs), responsible for tumor recurrence and resistance to current cancer therapies. Therefore, in-depth identification of TME and development of more potent CAR platform targeting CSCs may overcome the raised challenges, as presented in this review. We also discuss recent stemness-based innovations in CAR T-cell production and engineering to improve their efficacy in vivo, and finally, we propose solutions and strategies such as oncolytic virus-based therapy and combination therapy to revive the function of CAR T-cell therapy, especially in TME of solid tumors in future.