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Abstract: Epilepsy and migraine are chronic neurological disorders with shared clinical as well as pathophysiological mechanisms. Epileptic patients are at a higher risk of developing migraine compared to normal individuals and vice versa. Several genetic and environmental risk factors have been reported to be associated with the development of both diseases. Previous studies have already established standard genetic markers involved in various pathways implicated in the pathogenesis of both these comorbid conditions. In addition to genetic markers, epigenetic markers have also been found to be involved in the pathogenesis of epilepsy and migraine. Among the epigenetic markers, miRNAs have been explored at length and have emerged as significant players in regulating the expression of their target genes. miRNAs like miR-22, miR-34a, miR-155, miR-211, and Let-7b play a significant role in neuronal differentiation and seem to be associated with epilepsy and migraine as comorbid conditions. However, the exact shared mechanisms underlying the role of these miRNAs in these comorbid conditions are still unclear. The current review has been compiled with an aim to explore common microRNAs targeting the genes involved in shared molecular pathways leading to epilepsy and migraine as comorbid conditions. The new class of ncRNAs, i.e., tRNA transfer fragments, are also discussed. In addition, their role as potential biomarkers and therapeutic targets has also been evaluated. However, limitations exist, and based on the current literature available, only a few microRNAs seem to be involved in the pathogenesis of both these disorders.

tRFs are small tRNA derived fragments that are emerging as novel therapeutic targets and regulatory molecules in the pathophysiology of various neurological disorders. These are derived from precursor or mature tRNA, forming different subtypes that have been reported to be involved in neurological disorders like stroke, Alzheimer's, epilepsy, Parkinson's, MELAS, autism, and Huntington's disorder. tRFs were earlier believed to be random degradation debris of tRNAs. The significant variation in the expression level of tRFs in disease conditions indicates their salient role as key players in regulation of these disorders. Various animal studies are being carried out to decipher their exact role; however, more inputs are required to transform this research knowledge into clinical application. Future investigations also call for high-throughput technologies that could help to bring out the other hidden aspects of these entities. However, studies on tRFs require further research efforts to overcome the challenges posed in quantifying tRFs, their interactions with other molecules, and the exact mechanism of function. In this review, we are abridging the current understanding of tRFs, including their biogenesis, function, relevance in clinical therapies, and potential as diagnostic and prognostic biomarkers of these neurological disorders.

Neurological diseases (NDs) are one of the leading causes of disability and the second leading cause of death globally. Among these stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are the most common NDs. A rise in the absolute number of individuals affected with these diseases indicates that the current treatment strategies in management and prevention of these debilitating diseases are not effective sufficiently. Therefore, novel treatment strategies are being explored to cure these diseases by addressing the causative mechanisms at the molecular level. Advanced therapies like gene therapy (gene editing and gene silencing) and stem cell therapies aim to cure diseases by gene editing, gene silencing and tissue regeneration, respectively. Gene editing results in the deletion of the aberrant gene or insertion of the corrected gene which can be executed using the CRISPR/Cas gene editing tool a promising treatment strategy being explored for many other prevalent diseases. Gene silencing using siRNA silences the gene by inhibiting protein translation, thereby silencing its expression. Stem cell therapy aims to regenerate damaged cells or tissues because of their ability to divide into any type of cell in the human body. Among these approaches, gene editing and gene silencing have currently been applied in vitro and to animal models, while stem cell therapy has reached the clinical trial stage for the treatment of NDs. The current status of these strategies suggests a promising outcome in their clinical translation.

Migraine is a neurological disorder defined by episodic attacks of chronic pain associated with nausea, photophobia, and phonophobia. It is known to be a complex disease with several environmental and genetic factors contributing to its susceptibility. Risk factors for migraine include head or neck injury (Arnold, Cephalalgia 38(1):1-211, 2018). Stress and high temperature are known to trigger migraine, while sleep disorders and anxiety are considered to be the comorbid conditions with migraine. Studies have reported various biomarkers, including genetic variants, proteins, and metabolites implicated in migraine's pathophysiology. Using the "omics" approach, which deals with genetics, transcriptomics, proteomics, and metabolomics, more specific biomarkers for various migraine can be identified. On account of its multifactorial nature, migraine is an ideal study model focusing on integrated omics approaches, including genomics, transcriptomics, proteomics, and metabolomics. The current review has been compiled with an aim to focus on the genomic alterations especially involved in the regulation of glutamatergic neurotransmission, cortical excitability, ion channels, solute carrier proteins, or receptors; their expression in migraine patients and also specific proteins and metabolites, including some inflammatory biomarkers that might represent the migraine phenotype at the molecular level. The systems biology approach holds the promise to understand the pathophysiology of the disease at length and also to identify the specific therapeutic targets for novel interventions.

Treatment of osteoarthritic patients requires the development of morphologically and mechanically complex hyaline cartilage at the injury site. A tissue engineering approach toward differentiating mesenchymal stem cells into articular chondrocytes has been developed to overcome the drawbacks of conventional therapeutic and surgical procedures. To imitate the native micro and macro environment of articular chondrocytes, cell culture parameters such as oxygen concentration, mechanical stress, scaffold design, and growth factor signalling cascade regulation must be addressed. This review aims to illuminate the path toward developing tissue engineering approaches, accommodating these various parameters and the role these parameters play in regulating chondrogenesis for better articular cartilage development to treat osteoarthritis effectively.

Accelerating cases of diabetes worldwide have given rise to higher incidences of diabetic complications. MiRNAs, a much-explored class of non-coding RNAs, play a significant role in the pathogenesis of diabetes mellitus by affecting insulin release, β-cell proliferation, and dysfunction. Besides, disrupted miRNAs contribute to various complications, diabetic retinopathy, nephropathy, and neuropathy as well as severe conditions like diabetic foot. MiRNAs regulate various processes involved in diabetic complications like angiogenesis, vascularization, inflammations, and various signaling pathways like PI3K, MAPK, SMAD, and NF-KB signaling pathways. Diabetic neuropathy is the most common diabetic complication, characterized mainly by pain and numbness, especially in the legs and feet. MiRNAs implicated in diabetic neuropathy include mir-9, mir-106a, mir-146a, mir-182, miR-23a and b, miR-34a, and miR-503. The diabetic foot is the most common diabetic neuropathy, often leading to amputations. Mir-203, miR-23c, miR-145, miR-29b and c, miR-126, miR-23a and b, miR-503, and miR-34a are associated with diabetic foot. This review has been compiled to summarize miRNA involved in initiation, progression, and miRNAs affecting various signaling pathways involved in diabetic neuropathy including the diabetic foot. Besides, potential applications of miRNAs as biomarkers and therapeutic targets in this microvascular complication will also be discussed.

Stroke is the second most common cause of death worldwide. It occurs due to the insufficient supply of oxygen-rich blood to the brain. It is a complex disease with multiple associated risk factors, including smoking, alcoholism, age, sex, ethnicity, etc. Calcium ions are known to play a vital role in cell death pathways, which is a ubiquitous intracellular messenger during and immediately after an ischemic period. Disruption in normal calcium homeostasis is known to be a major initiator and activator of the ischemic cell death pathway. Under ischemic stroke conditions, glutamate is released from the neurons and glia, which further activates the N-methyl-D-aspartate (NMDA) receptor and triggers the rapid translocation of Ca2+ from extracellular to intracellular spaces in cerebral tissues and vice versa. Various studies indicated that Ca2+ could have harmful effects on neurons under acute ischemic conditions. Mitochondrial dysfunction also contributes to delayed neuronal death, and it was established decades ago that massive calcium accumulation triggers mitochondrial damage. Elevated Ca2+ levels cause mitochondria to swell and release their contents. As a result, oxidative stress and mitochondrial calcium accumulation activate mitochondrial permeability transition and lead to depolarization-coupled production of reactive oxygen species. This association between calcium levels and mitochondrial death suggests that elevated calcium levels might have a role in the neurological outcome in ischemic stroke. Previous studies have also reported that elevated Ca2+ levels play a role in the determination of infarct size, outcome, and recurrence of ischemic stroke. The current review has been compiled to understand the multidimensional role of altered Ca2+ levels in the initiation and alteration of neuronal death after an ischemic attack. The underlying mechanisms understood to date have also been discussed.

Heliotropium indicum Linn., a plant also known as 'Indian heliotrope,' is found in tropical and temperate regions of the world, and throughout India. This plant exhibits varieties of therapeutic effects like anti-inflammatory, anti-bacterial, anti-fertility, anti-nociceptive, and anti-tumor activities. In addition, the Heliotropium indicum L. plant have been reported to have therapeutic effects in kidney stone or urolithiasis. But it is not reported to date which phytochemicals are responsible for it. The current studies deal with multi-targets-based virtual screening for identification of the phytochemicals found in Heliotropium indicum L. leaves against different targets including antioxidants and anti-urolithiatic proteins. From the molecular docking-based screening, it was found that phytochemicals Pestalamide B, Rapanone, and Supinine possess had excellent binding modes against the targets selected for urolithiasis activities. However, 3`-Acetyl lycopsamine, Trachelanthamine, Lycopsamine, Heliotrine, Rinderine, Echinatine exhibited the binding modes with some anti-urolithiasis targets only along with all the antioxidant targets. Therefore, these phytochemicals from Heliotropium indicum L. leaves were found to have high potential in urolithiasis, but need to be proved experimentally. These phytochemicals are never reported against urolithiasis or kidney stone to date. Therefore, the results of the current studies can be exploited further for designing and discovering new anti-urolithiasis agents for the treatment of kidney stone/urolithiasis.

Background Platelets play a significant role in pathophysiology of ischemic stroke since they are involved in the formation of intravascular thrombus after erosion or rupture of the atherosclerotic plaques. Platelet (PLT) count and Mean platelet volume (MPV) are the two significant parameters that affect functions of the platelets. Methods In the current study MPV and PLT count was evaluated using flow cytometry and cell counter. SonoClot analysis was carried out to evaluate Activated Clot Timing (ACT), Clot Rate (CR) and Platelet Function (PF). Genotyping was carried out GSA and Sanger sequencing and expression analysis was carried out using RT-PCR. In silico analysis was carried out using GROMACS tool and UNAFold. The interaction of significant proteins with other proteins was predicted using STRING database. Results 96 genes were analyzed and a significant association of THPO (rs6141) and ARHGEF3 (rs1354034) was observed with the disease and its subtypes. Altered genotypes were associated significantly with increased MPV, decreased PLT count and CR. Expression analysis revealed a higher expression in patients bearing the variant genotypes of both the genes. In silico analysis revealed that mutation in THPO gene leads to the reduced compactness of protein structure. mRNA encoded by mutated ARHGEF3 gene increases the half-life of mRNA. The two significant proteins interact with many other proteins especially the ones involved in the platelet activation, aggregation, erythropoiesis, megakaryocyte maturation, and cytoskeleton rearrangements suggesting that they could be important player in determination of MPV values. Conclusions In conclusion the current study demonstrated the role of higher MPV affected by genetic variation in the development of IS and its subtypes. The results of the current study also indicate that higher MPV can be used as a biomarker for the disease and altered genotypes and higher MPV can be targeted for better therapeutic outcomes.

Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs' role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review.

Background: Epilepsy is one of the prevalent neurological disorders characterized by disrupted synchronization between inhibitory and excitatory neurons. Disturbed membrane potential due to abnormal regulation of neurotransmitters and ion transport across the neural cell membrane significantly contributes to the pathophysiology of epilepsy. Potassium ion channels (KCN) regulate the resting membrane potential and are involved in neuronal excitability. Genetic alterations in the potassium ion channels (KCN) have been reported to result in the enhancement of the release of neurotransmitters, the excitability of neurons, and abnormal rapid firing rate, which lead to epileptic phenotypes, making these ion channels a potential therapeutic target for epilepsy. The aim of this study is to explore the variations reported in different classes of potassium ion channels (KCN) in epilepsy patients, their functional evaluation, and therapeutic strategies to treat epilepsy targeting KCN. Methodology: A review of all the relevant literature was carried out to compile this article. Result: A large number of variations have been reported in different genes encoding various classes of KCN. These genetic alterations in KCN have been shown to be responsible for disrupted firing properties of neurons. Antiepileptic drugs (AEDs) are the main therapeutic strategy to treat epilepsy. Some patients do not respond favorably to the AEDs treatment, resulting in pharmacoresistant epilepsy. Conclusion: Further to address the challenges faced in treating epilepsy, recent approaches like optogenetics, chemogenetics, and genome editing, such as clustered regularly interspaced short palindromic repeats (CRISPR), are emerging as target-specific therapeutic strategies.

Discoidin domain receptors, DDR1 and DDR2 are members of the receptor tyrosine kinase (RTK) family that serves as a non-integrin collagen receptor and were initially identified as critical regulators of embryonic development and cellular homeostasis. In recent years, numerous studies have focused on the role of these receptors in disease development, in particular, cancer where they have been reported to augment ECM remodeling, invasion, drug resistance to facilitate tumor progression and metastasis. Interestingly, accumulating evidence also suggests that DDRs promote apoptosis and suppress tumor progression in various human cancers due to which their functions in cancer remain ill-defined and presents a case of an interesting therapeutic target. The present review has discussed the role of DDRs in tumorigenesis and the metastasis.

An emerging component of Unfolded Protein Response (UPR) pathway, cation transport regulator homolog 1 (CHAC1) has been conferred with the ability to degrade intracellular glutathione and induce apoptosis, however, many reports have suggested a role of CHAC1 in cancer progression. Our study aimed to investigate CHAC1 mRNA levels in large breast cancer datasets using online tools and both mRNA and protein levels in different breast cancer cell lines.Analysis of clinical information from various online tools (UALCAN, GEPIA2, TIMER2, GENT2, UCSCXena, bcGenExMiner 4.8, Km Plotter, and Enrichr) was done to elucidate the CHAC1 mRNA expression in large breast cancer patient dataset and its correlation with disease progression. Later, in vitro techniques were employed to explore the mRNA and protein expression of CHAC1 in breast cancer cell lines. Evidence from bioinformatics analysis as well as in vitro studies indicated a high overall expression of CHAC1 in breast tumor samples and had a significant impact on the prognosis and survival of patients. Enhanced CHAC1 levels in the aggressive breast tumor subtypes such as Human Epidermal growth factor receptor 2 (HER2) and Triple Negative Breast Cancer (TNBC) were evident. Our findings hint toward the possible role of CHAC1 in facilitating the aggressiveness of breast cancer and the disease outcome.In summary, CHAC1 is constantly up-regulated in breast cancer leading to a poor prognosis. CHAC1, therefore, could be a promising candidate in the analysis of breast cancer diagnosis and prognosis.

Background: The capsid coated protein of Bluetongue virus (BTV) VP2 is responsible for BTV transmission by the Culicoides vector to vertebrate hosts. Besides, VP2 is responsible for BTV entry into permissive cells and hence plays a major role in disease progression. However, its mechanism of action is still unknown. Objective: The present investigation aimed to predict the 3D structure of Viral Protein 2 of the bluetongue virus assisted by Optimized Potential for Liquid Simulations (OPLS), structure validation, and an active site prediction. Methods: The 3D structure of the VP2 protein was built using a Python-based Computational algorithm. The templates were identified using Smith waterman’s Local alignment. The VP2 protein structure validated using PROCHECK. Molecular Dynamics Simulation (MDS) studies were performed using an academic software Desmond, Schrodinger dynamics, for determining the stability of a model protein. The Ligand-Binding site was predicted by structure comparison using homology search and proteinprotein network analysis to reveal their stability and inhibition mechanism, followed by the active site identification. Results: The secondary structure of the VP2 reveals that the protein contains 220 alpha helix atoms, 40 310 helix, 151 beta sheets, 134 coils and 424 turns, whereas the 3D structure of Viral Protein 2 of BTV has been found to have 15774 total atoms in the structure. However, 961 amino acids were found in the final model. The dynamical cross-correlation matrix (DCCM) analysis tool identifies putative protein domains and also confirms the stability of the predicted model and their dynamical behavior difference with the correlative fluctuations in motion. Conclusion: The biological interpretation of the Viral Protein 2 was carried out. DCCM maps were calculated, using a different coordinate reference frame, through which, protein domain boundaries and protein domain residue constituents were identified. The obtained model shows good reliability. Moreover, we anticipated that this research should play a promising role in the identification of novel candidates with the target protein to inhibit their functional significance.

Increasing herbal formulations have been used to treat several diseases including cancer. W. somnifera (Ashwagandha) is one such plant the extracts of which have been tested against a number of ailments including cancer, which remains as one of the most dreadful diseases on the globe. The ever-increasing number of cancer related mortality demands the development of novel chemopreventive agents with minimum side effects. Different compounds isolated from various parts of the plant like root, stem, and leaves have been reported to display significant anti-cancerous and immunomodulating properties and thus can be used alone or in combination with other chemotherapeutic drugs for cancer treatment. Through this review, we highlight the importance of W. somnifera in countering the potential oncogenic signaling mediators that are modulated by active constituents of W. somnifera in a variety of cancer types. Further, we hope that active constituents of W. somnifera will be tested in clinical trials so that they can be used as an important adjuvant in the near future for the effective treatment of cancer.

Imidazole-based epidermal growth factor receptor (EGFR) inhibitors were computationally designed and synthesized. All the compounds were assessed for their anti-proliferative activity against five cancer cell lines, viz., MDA-MB-231 (breast), T47D (breast) and MCF-7 (breast), A549 (lung) and HT-29 (colorectal). Compounds 2c and 2d emerged as better anticancer molecules with no toxicity towards normal cells. 2c and 2d inhibited EGFR enzymatic activity in vitro with IC50 values of 617.33 ± 0.04 nM and 710 ± 0.05 nM, respectively. In order to further improve the potency, we explored an unoccupied area of the ATP binding domain of EGFR and analysed an in silico interaction model of 2c and 2d-EGFR complexes that guided and allowed substitution of the 4-fluorophenyl ring (2c and 2d) with 4-(4-methylpiperazinyl)-3-nitrophenyl at the N-9 position, resulting in compound 3c with a better binding score and potent EGFR inhibitory activity (IC50: 236.38 ± 0.04 nM), which was comparable to the positive control erlotinib (239.91 ± 0.05 nM). 3c exhibited a great improvement in anticancer potency with inhibition of cell growth of all cancer cell lines at very low micromolar concentrations (IC50 = 1.98 to 4.07 μM). Further investigation revealed that 3c also induced an increase in ROS levels in cancer cells in a mitochondrial-independent manner and halted the cell cycle at the sub-G1 phase.

Type 2 Diabetes mellitus (T2DM) is a multifactorial metabolic disorder also known as a silent killer disease. Macrovascular and microvascular complications associated with diabetes worsen the condition leading to higher comorbidity and mortality rate. Currently, available treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4 (dipeptidyl-peptidase-4) inhibitors, SGLT-2 inhibitors, and Glucagon Like Peptide-1 receptor agonists (GLP-1RAs). Synthetic agonists of GLP-1 hormone, GLP-1RAs are an emerging class of anti-diabetic drugs which target the pathophysiology of diabetes through various mechanisms and at multiple sites. They promote insulin secretion from beta cells, and the proliferation of beta cells inhibits glucagon secretion, delays gastric emptying and induces satiety. However, treatment is reported to be associated with inter-individual variations and adverse drug reactions, which are also influenced by genetic variations. There have been a few pharmacogenetic studies have been carried out on this drug class. This review discusses all the available GLP-1RAs, their pharmacokinetics, pharmacodynamics and genetic variation affecting the inter-individual variation.

Protein-protein interactions (PPI) are pivotal to the numerous processes in the cell. Therefore, it is of interest to document the analysis of these interactions in terms of binding sites, topology of the interacting structures and physiochemical properties of interacting interfaces and the of forces interactions. The interaction interface of obligatory protein-protein complexes differs from that of the transient interactions. We have created a large database of protein-protein interactions containing over100 thousand interfaces. The structural redundancy was eliminated to obtain a non-redundant database of over 2,265 interaction interfaces. Therefore, it is of interest to document the analysis of these interactions in terms of binding sites, topology of the interacting structures and physiochemical properties of interacting interfaces and the offorces interactions. The residue interaction propensity and all of the rest of the parametric scores converged to a statistical indistinguishable common sub-range and followed the similar distribution trends for all three classes of sequence-based classifications PPInS. This indicates that the principles of molecular recognition are dependent on the preciseness of the fit in the interaction interfaces. Thus, it reinforces the importance of geometrical and electrostatic complementarity as the main determinants for PPIs.

Breast cancer is a multifactorial, heterogeneous disease and the second most frequent cancer amongst women worldwide. Metastasis is one of the most leading causes of death in these patients. Early-stage or locally advanced breast cancer is limited to the breast or nearby lymph nodes. When breast cancer spreads to farther tissues/organs from its original site, it is referred to as metastatic or stage IV breast cancer. Normal breast development is regulated by specific genes and signalling pathways controlling cell proliferation, cell death, cell differentiation and cell motility. Dysregulation of genes involved in various signalling pathways not only leads to the formation of primary tumour but also to the metastasis as well. The metastatic cascade is represented by a multi-step process including invasion of the local tumour cell followed by its entry into the vasculature, exit of malignant cells from the circulation and ultimately their colonization at the distant sites. These stages are referred to as formation of primary tumour, angiogenesis, invasion, intravasation and extravasation, respectively. The major sites of metastasis of breast cancer are the lymph nodes, bone, brain and lung. Only about 28% five-year survival rate has been reported for stage IV breast cancer. Metastasis is a serious concern for breast cancer and therefore, various therapeutic strategies such as tyrosine kinase inhibitors have been developed to target specific dysregulated genes and various signalling pathways involved in different steps of metastasis. In addition, other therapies like hyperbaric oxygen therapy, RNA interference and CRISPR/Cas9 are also being explored as novel strategies to cure the stage IV/metastatic breast cancer. Therefore, the current review has been compiled with an aim to evaluate the genetic basis of stage IV breast cancer with a focus on the molecular mechanisms. In addition, the therapeutic strategies targeting these dysregulated genes involved in various signalling pathways have also been discussed. Genome editing technologies that can target specific genes in the affected areas by making knock-in and knock-out alternations and thereby bring significant treatment outcomes in breast cancer have also been summarized.

A worldwide failure to achieve glycemic targets has led to complications associated with diabetes mellitus. In addition to genetic and other risk factors, epigenetic factors like DNA methylation, histone modifications, and non-coding RNAs play a significant part in the pathogenesis of complications. Among non-coding RNAs, miRNAs have been explored extensively since they control various biological processes. Their dysregulation has been implicated in various diseases including diabetic complications. Diabetic retinopathy and nephropathy are two common microvascular diabetic complications. Diabetic retinopathy affects the retina of the eye whereas nephropathy damages kidneys on account of prolonged hyperglycemia. This review aims to evaluate the role of miRNAs in diabetic retinopathy and diabetic nephropathy with an emphasis on the dysregulation of various pathways involved. In addition, the role of significant miRNAs as biomarkers for the diagnosis and prognosis of complications has also been discussed. Further, an update on the role of important miRNAs as potential therapeutic modalities has been given.

Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared.Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients.Elevated levels of CRP were found among the diseased in comparison with controls (P0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)].Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high.

Background: Malaria, one of the World’s biggest billers’ is on the schedule for biomedical research and public health policies. The introduction of the artemisinin, a Chinese traditional drug from Artemisia annua is a revolution in the treatment of malaria. Artemisinin-based combination treatment (ACT) is considered to be the best strategy for uncomplicated Falciparum malaria. The presence of 1,2,4-trioxane system in artemisinin is responsible for its antimalarial activity. Methods: In this study, twenty-nine analogues of artemisinin were taken into account for QSAR studies along with artemisinin. The most active analogue of artemisinin 21 was energy minimized. All the structures were prepared from the active conformer 21 and energy was minimized to the stable state using MMFF94 force field using ChemBioDraw-12. Genetic Algorithm is used to decide the descriptors best required for the model generation. The test set and training set division were done by using hierarchal clustering module available with NCSS statistical software. Results and Conclusion: The antimalarial activity of the artemisinin and its substituted analogues has been analyzed through the multiple linear regression (MLR) using various physiochemical and structural descriptors obtained from PADEL software. The models were prepared using the Sigma Plot version 11. The calculated 2D autocorrelation descriptors and the MLR model suggest that artemisinin and its analogues hold the scope in the optimization of antimalarial activity.

Increasing herbal formulations have been used to treat several diseases including cancer.

Epilepsy and migraine are both episodic disorders and share clinical as well as pathophysiological mechanisms. The prevalence of epilepsy in migraine patients is generally higher than normal as compared to general population and vice versa. Various environmental risk factors and genetic factors have been reported to be associated with susceptibility of these comorbid diseases. Specific genes have been implicated in the pathogenesis of the two diseases. However, the shared genetic susceptibility has not been explored extensively. Previous studies have reported that the alterations in the genes encoding ion channel proteins are common risk factors for both the diseases. The alterations in ion channel-encoding genes CACNAIA (T666M) and SCNIA (Q1489K and L1649Q) have been found to be involved in the development of familial hemiplegic migraine (FHM) as well as generalized epilepsy and some cases of focal epilepsy as well. The fact that both these disorders are treated with anti-epileptic drugs (AEDs) strongly supports common underlying mechanisms. This review has been compiled with an aim to explore the alterations in common genes involved in various pathways regulating neuronal hyperexcitability, a common risk factor for both these conditions. The avenue for future treatment strategies targeting common genes and molecular mechanisms has also been discussed.

Human epidermal growth factor receptor (HER2) is a well-established histopathological marker. It is aberrantly expressed in various cancers, predominantly in breast cancer. HER2 protein overexpression and/or HER2 gene amplification induces HER2 dimerization, tyrosine kinase (TK) phosphorylation, activation of different signaling pathways including the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, and hence, carcinogenesis. HER2 antibodies like trastuzumab and pertuzumab act on the extracellular domain (ECD) of the HER2 receptor. These were developed to treat HER2-overexpressing or amplified cancers. These effectively inhibit HER2 dimerization and, hence, further signaling. However, antibody resistance and, thereby, disease relapse have emerged as serious concerns. HER2 splicing, cross-signaling, and intracellular alterations are the most common factors causing HER2-antibody resistance. To overcome the therapeutic resistance associated with trastuzumab, TK inhibitors (TKIs) were developed. These bind to the intracellular TK domain and inhibit TK phosphorylation and, therefore, signaling. Though less selective, TKIs have been reported to show activity against HER2 spliced variants and inhibit breast cancers resistant to HER2 antibodies. However, these have not really been established as monotherapeutic agents and have remained as alternative therapeutics only on the account of resistance, toxicity, and poor pharmacokinetic profile. These issues can be resolved by employing combination treatment regimens including HER2-antibody and HER2 TKI. The HER2 TKI in conjunction with HER2 antibody sensitize the refractory HER2-positive cancers towards HER2-anti-body therapy. In addition, these act synergistically with the HER2-antibody resulting in an additive clinical response in patients. This chapter will explore various HER2 TKIs- lapatinib, neratinib, afatinib, sapitinib, CP-724,714, dacomitinib, tucatinib, pyrotinib, and poziotinib as promising clinical tools in sensitizing resistant cancers to HER2 antibodies.