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Abstract Patient‐derived xenografts (PDX) involve transplanting patient cells or tissues into immunodeficient mice, offering superior disease models compared with cell line xenografts and genetically engineered mice. In contrast to traditional cell‐line xenografts and genetically engineered mice, PDX models harbor the molecular and biologic features from the original patient tumor and are generationally stable. This high fidelity makes PDX models particularly suitable for preclinical and coclinical drug testing, therefore better predicting therapeutic efficacy. Although PDX models are becoming more useful, the several factors influencing their reliability and predictive power are not well understood. Several existing studies have looked into the possibility that PDX models could be important in enhancing our knowledge with regard to tumor genetics, biomarker discovery, and personalized medicine; however, a number of problems still need to be addressed, such as the high cost and time‐consuming processes involved, together with the variability in tumor take rates. This review addresses these gaps by detailing the methodologies to generate PDX models, their application in cancer research, and their advantages over other models. Further, it elaborates on how artificial intelligence and machine learning were incorporated into PDX studies to fast‐track therapeutic evaluation. This review is an overview of the progress that has been done so far in using PDX models for cancer research and shows their potential to be further improved in improving our understanding of oncogenesis.

Abstract Therapeutic effect of phytochemicals has been emphasized in the traditional medicine owing to the presence of bioactive molecules, such as polyphenols. Luteolin is a flavone belonging to the flavonoid class of polyphenolic phytochemicals with healing effect on hypertension, inflammatory disorders, and cancer due to its action as pro-oxidants and antioxidants. The anticancer profile of luteolin is of interest due to the toxic effect of contemporary chemotherapy paradigm, leading to the pressing need for the development and identification of physiologically benevolent anticancer agents and molecules. Luteolin exerts anticancer activity by downregulation of key regulatory pathways associated with oncogenesis, in addition to the induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells. In this review, we discuss about the anticancer profile of luteolin.

Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology.

In the modern era, cancer can be controlled by chemotherapy treatment, and in many situations a stable disease is obtained. The significant clinical success and subsequent commercialization of naturally derived molecules have further encouraged their exploration as adjunctive therapies in cancer management. The purpose of this comprehensive review is to update the anticancer mechanisms triggered by Erinacine A and regulation of signaling pathways potentially involved in its anticancer activity.The results of preclinical research showed that Erinacin A, a therapeutically important biological metabolite isolated from the basidiomycete fungus Hericium erinaceus offers a multitude of possible chemotherapeutic applications by regulating complex signaling pathways as validated by various pharmacological in vitro and in vivo studies. As a result of Erinacin A's action on oncological signaling pathways, it resulted in induction of apoptosis, reduction of proliferation, invasiveness, generation of oxidative stress and cell cycle arrest in cancer cells.

Nanoliposomes are bilayer phospholipid vesicles used to encapsulate and deliver therapeutic agents. The study was aimed to investigate the effects of critical variables on nanoliposomes characteristics. Imatinib mesylate-loaded nanoliposomes were formulated by the two-step emulsification process using a high-speed homogenizer system and probe-type ultrasonicator. The Box-Behnken design was utilized to optimize the process parameters. The mean particle size of nanoliposomes was found to be 211 nm to 623.3 nm with a low value of polydispersity index (0.005 to 0.7). Zeta potential values varied from ‒27.6 mV to ‒9.2 mV in uncoated nanoliposomes to +27.5 mV in chitosan-coated nanoliposomes. The encapsulation efficiency in formulation NLP-H8 containing 200 mg of phosphatidylcholine, homogenization speed of 12000 rpm, and 7 min of sonication time was found to be 76.49% without the coating and 85.4% in 0.2% w/v chitosan-coated nanoliposomes. TEM image confirmed the spherical shape of nanoliposomes. In-vitro drug release study demonstrated that the optimized nanoliposomal formulations released 84.67% of the loaded drug after 24 h in 0.1 N HCl. The IC50 value of formulation NLP-H8 was found to be 7.98 μM. Nanoliposomal formulations were prepared successfully with suitable size, morphology, encapsulation efficiency, and drug release. The models developed in this study may be utilized further as a response surface for the various parameters of nanoliposomes.

Background: Curcumin and quercetin are the two important flavonoids that are being used as food ingredients across the globe. They also possess many pharmacological activities such as anti-inflammatory, anticancer and antidiabetic activity. The combination of both these phytoconstituents is available in the market. However, there is lack of any suitable analytical method reported for their simultaneous estimation in food as well as pharmaceutical products. Hence, there is a need to develop a simultaneous method for them. Objectives: The study aims to develop and validate a simple high-performance liquid chromatography (HPLC) method for the simultaneous determination of curcumin and quercetin. Method: Gradient elution was carried out in ACN and GAA (2% v/v) for 15 min wherein the ratio of ACN and GAA was varied from 40-60 v/v ACN: 60-40 GAA v/v from 0-5 min followed by 60-80 v/v ACN: 40-20 v/v GAA between 7- 10 min followed by 80 % ACN: 20 % GAA between 10-15 min. The flow rate was kept 1 mL/min and detection wavelength at 395 nm. The method has been validated according to International Conference of Harmonization (ICH) Q2 (R1) guidelines with respect to specificity, system suitability, accuracy, precision, and robustness. The developed method was further used for the determination of curcumin and quercetin in different herbal extracts, marketed formulations containing these drugs and developed self-nano emulsifying drug delivery system (SNEDDS). Results: The method was linear in the concentration range of 50-250 ng mL-1 for curcumin and 800-1600 ng mL?1 for quercetin, respectively. The limit of detection (LOD) and limit of quantification (LOQ) were 11.76 and 35.6 ng mL?1 for curcumin, respectively, while LOD and LOQ for quercetin were 32.94 and 99.76 ng/mL?1, respectively. The percentage recovery that was found to be in the range of 95-105% with relative standard deviation less than 2% indicating the accuracy and precision of method for both the drugs. Further, the validated method was found specific to detect presence of both the drugs in extracts, marketed formulations and developed SNEDDS. Conclusions: The developed method showed excellent specificity, linearity, accuracy and precision. Thus, it can be further explored to detect curcumin and quercetin in biological samples as well as other marketed formulations.

Developmental signalling pathways such as Wnt/β-catenin, Notch and Sonic hedgehog play a central role in nearly all the stages of neuronal development. The term ‘embryonic’ might appear to be a misnomer to several people because these pathways are functional during the early stages of embryonic development and adulthood, albeit to a certain degree. Therefore, any aberration in these pathways or their associated components may contribute towards a detrimental outcome in the form of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke. In the last decade, researchers have extensively studied these pathways to decipher disease-related interactions, which can be used as therapeutic targets to improve outcomes in patients with neurological abnormalities. However, a lot remains to be understood in this domain. Nevertheless, there is strong evidence supporting the fact that embryonic signalling is indeed a crucial mechanism as is manifested by its role in driving memory loss, motor impairments and many other processes after brain trauma. In this review, we explore the key roles of three embryonic pathways in modulating a range of homeostatic processes such as maintaining blood–brain barrier integrity, mitochondrial dynamics and neuroinflammation. In addition, we extensively investigated the effect of these pathways in driving the pathophysiology of a range of disorders such as Alzheimer's, Parkinson's and diabetic neuropathy. The concluding section of the review is dedicated to neurotherapeutics, wherein we identify and list a range of biological molecules and compounds that have shown enormous potential in improving prognosis in patients with these disorders.

Abstract Background Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post‐translational level. Skp, Cullin, F‐box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three‐dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable “super‐enzymatic” process that might respond to targeted therapeutic modalities in cancer. Recent findings Several F‐box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F‐box members like βTrcP1 and βTrcP2, the ones with context‐dependent functionality, have also been studied and reported. FBXW7 is a well‐studied F‐box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c‐Myc, cyclin E, mTOR, c‐Jun, NOTCH, myeloid cell leukemia sequence‐1 (MCL1), AURKA, NOTCH through the well‐known ubiquitin‐proteasome system (UPS)‐mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half‐life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7‐NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation‐related events, cell cycle, proliferation, apoptosis, and metastasis. Conclusion The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7‐NOTCH aberrations in tumors.

Abstract Polyindole-based hybrid composites are being recognized as a promising candidate to be used in energy storage field along with other conjugated organic polymers. Polyindoles themselves are affected with low electrical and electrochemical conductivity; nevertheless, high redox activity, tunable electrical conductivity, significant thermal stability, slow degradation rate, and possible blending property give them upper hand to be used as a good contender. Certain factors viz. electrolyte, concentration, morphology, pH, temperature, etc., are major components affecting performance of Polyindole and its composites. This assessment recapitulates the position of Polyindole and its hybrid composite to be used as energy harvest material; in addition, this evaluation also pronounces the future aspect of the hybrids.

The inflammatory response is a central aspect of the human immune system that acts as a defense mechanism to protect the body against infections and injuries. A dysregulated inflammatory response is a major health concern, as it can disrupt homeostasis and lead to a plethora of chronic inflammatory conditions. These chronic inflammatory diseases are one of the major causes of morbidity and mortality worldwide and the need for them to be managed in the long term has become a crucial task to alleviate symptoms and improve patients’ overall quality of life. Although various synthetic anti-inflammatory agents have been developed to date, these medications are associated with several adverse effects that have led to poor therapeutic outcomes. The hunt for novel alternatives to modulate underlying chronic inflammatory processes has unveiled nature to be a plentiful source. One such example is agarwood, which is a valuable resinous wood from the trees of Aquilaria spp. Agarwood has been widely utilized for medicinal purposes since ancient times due to its ability to relieve pain, asthmatic symptoms, and arrest vomiting. In terms of inflammation, the major constituent of agarwood, agarwood oil, has been shown to possess multiple bioactive compounds that can regulate molecular mechanisms of chronic inflammation, thereby producing a multitude of pharmacological functions for treating various inflammatory disorders. As such, agarwood oil presents great potential to be developed as a novel anti-inflammatory therapeutic to overcome the drawbacks of existing therapies and improve treatment outcomes. In this review, we have summarized the current literature on agarwood and its bioactive components and have highlighted the potential roles of agarwood oil in treating various chronic inflammatory diseases.

Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep–wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual’s circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.