Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy.

Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.

GAS5 lncRNA: A biomarker and therapeutic target in breast cancer.

Breast cancer is one of the most common causes of cancer-related mortality globally, and its aggressive phenotype results in poor treatment outcomes. Growth Arrest-Specific 5 long non-coding RNA has attracted considerable attention due to its pivotal function in apoptosis regulation and tumor aggressiveness in breast cancer. Gas5 enhances apoptosis by regulating apoptotic proteins, such as caspases and BCL2 family proteins, and the sensitivity of BCCs to chemotherapeutic agents. At the same time, low levels of GAS5 increased invasion, metastasis, and overall tumor aggressiveness. GAS5 also regulates EMT markers, critical for cancer metastasis, and influences tumor cell proliferation by regulating various signaling components. As a result, GAS5 can be restored to suppress tumor development as a possible therapeutic strategy, which might present promising prospects for a patient's treatment. Its activity levels might also be a crucial indicator and diagnostic parameter for prediction. This review highlights the significant role of GAS5 in modulating apoptosis and tumor aggressiveness in breast cancer, emphasizing its potential as a therapeutic target for breast cancer treatment and management.

Exploring ncRNAs in epilepsy: From oxidative stress regulation to therapy.

Epilepsy is a prevalent neurological illness which is linked with high worldwide burdens. Oxidative stress (OS) is recognized to be among the contributors that trigger the advancement of epilepsy, affecting neuronal excitability and synaptic transmission. Various types of non-coding RNAs (ncRNAs) are known to serve vital functions in many disease mechanisms, including epilepsy. The current review sought to understand better the mechanisms through which these ncRNAs regulate epilepsy's OS-related pathways. We investigated the functions of microRNAs in controlling gene expression at the post-translatory stage and their involvement in OS and neuroinflammation. We also looked at the different regulatory roles of long ncRNAs, including molecular scaffolding, enhancer, and transcriptional activator, during OS. Circular RNAs and their capability to act as miRNA decoys and their consequential impact on epilepsy development were also explored. Our review aimed to improve the current understanding of novel therapies for epilepsy based on the role of ncRNAs in OS pathways. We also demonstrated the roles of ncRNAs in epilepsy treatment and diagnosis, explaining that these molecules play vital roles that could be used in therapy as biomarkers.

Detailed role of SR-A1 and SR-E3 in tumor biology, progression, and therapy.

The first host defense systems are the innate immune response and the inflammatory response. Among innate immune cells, macrophages, are crucial because they preserve tissue homeostasis and eradicate infections by phagocytosis, or the ingestion of particles. Macrophages exhibit phenotypic variability contingent on their stimulation state and tissue environment and may be detected in several tissues. Meanwhile, critical inflammatory functions are played by macrophage scavenger receptors, in particular, SR-A1 (CD204) and SR-E3 (CD206), in a variety of pathophysiologic events. Such receptors, which are mainly found on the surface of multiple types of macrophages, have different effects on processes, including atherosclerosis, innate and adaptive immunity, liver and lung diseases, and, more recently, cancer. Although macrophage scavenger receptors have been demonstrated to be active across the disease spectrum, conflicting experimental findings and insufficient signaling pathways have hindered our comprehension of the molecular processes underlying its array of roles. Herein, as SR-A1 and SR-E3 functions are often binary, either protecting the host or impairing the pathophysiology of cancers has been reviewed. We will look into their function in malignancies, with an emphasis on their recently discovered function in macrophages and the possible therapeutic benefits of SR-A1 and SR-E3 targeting.

Shedding Light on the Role of Exosomal PD-L1 (ExoPD-L1) in Cancer Progression: an Update.

Exosomes are the primary category of extracellular vesicles (EVs), which are lipid-bilayer vesicles with biological activity spontaneously secreted from either normal or tansformed cells. They serve a crucial role for intercellular communication and affect extracellular environment and the immune system. Tumor-derived exosomes (TEXs) enclose high levels of immunosuppressive proteins, including programmed death-ligand 1 (PD-L1). PD-L1 and its receptor PD-1 act as crucial immune checkpoint molecules, thus facilitating tumor advancement by inhibiting immune responses. PDL-1 is abundantly present on tumor cells and interacts with PD-1 on activated T cells, resulting in T cell suppression and allowing immune evasion of cancer cells. Various FDA-approved monoclonal antibodies inhibiting the PD-1/PD-L1 interaction are commonly used to treat a diverse range of tumors. Although the achieved results are significant, some individuals have a poor reaction to PD-1/PD-L1 blocking. PD-L1-enriched TEXs may mimic the impact of cell-surface PD-L1, consequently potentiating tumor resistance to PD1/PD-L1 based therapy. In light of this, a strong correlation between circulating exosomal PD-L1 levels and response rate to anti-PD-1/PD-L1 antibody treatment has been evinced. This article inspects the function of exosomal PDL-1 in developing resistance to anti-PD-1/PD-L1 therapy for opening new avenues for overcoming tumor resistance to such modalities and development of more favored combination therapy.

Beneficial Effects of PIN1 Inhibition on Diabetes Mellitus: A Concise Review.

Type 2 diabetes mellitus is a long-term medical illness in which the body either becomes resistant to insulin or fails to produce it sufficiently. Mostly, combinatorial therapy is required to control blood glucose levels. However, combinatorial therapy has detrimental side effects. The prevalence of the cases and subsequent increases in medical costs of the same intimidate human health globally. While there have been a lot of studies focused on developing diabetic regimens that work to lower blood glucose levels, their effectiveness is short-lived because of unfavorable side effects, such as weight gain and hypoglycemia. In recent years, the PIN1 (protein interacting with NIMA) enzyme has attracted the attention of researchers. Previous studies suggested that PIN1 may act on the various substrates that are involved in the progression of T2DM and also help in the management of diabetes-related disorders. Thus, the focus of the current review is to examine the correlation between PIN1, T2DM and its related disorders and explore the possibility of developing novel therapeutic targets through PIN1 inhibition.

Targeting the Wnt/ß-catenin cascade in osteosarcoma: The potential of ncRNAs as biomarkers and therapeutics.

Osteosarcoma (OS) is a bone cancer which stems from several sources and presents with diverse clinical features, making evaluation and treatment difficult. Chemotherapy tolerance and restricted treatment regimens hinder progress in survival rates, requiring new and creative therapeutic strategies. The Wnt/ß-catenin system has been recognised as an essential driver of OS development, providing potential avenues for therapy. Non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), are essential in modulating the Wnt/ß-catenin cascade in OS. MiRNAs control the system by targeting vital elements, while lncRNAs and circRNAs interact with system genes, impacting OS growth and advancement. This paper thoroughly analyses the intricate interplay between ncRNAs and the Wnt/ß-catenin cascade in OS. We examine how uncontrolled levels of miRNAs, lncRNAs, and circRNAs lead to an abnormal Wnt/ß-catenin network, which elevates the development, spread, and susceptibility to the treatment of OS. We emphasise the potential of ncRNAs as diagnostic indicators and avenues for treatment in OS care. The review offers valuable insights for academics and clinicians studying OS aetiology and creating new treatment techniques for the ncRNA-Wnt/ß-catenin cascade. Utilising the oversight roles of ncRNAs in the Wnt/ß-catenin system shows potential for enhancing the outcomes of patients and progressing precision medicine in OS therapy.

Metabolic causes of pediatric developmental & epileptic encephalopathies (DEE)- genetic variant analysis in a south Indian cohort.

PURPOSE: Drug-resistant epilepsy is seen in patients with inborn errors of metabolism and metabolic dysfunction in neurons is crucial to brain disorders associated with psychomotor impairment. Diagnostic rates of metabolic causes of developmental and epileptic encephalopathy (DEE) using next generation sequencing have been rarely studied in literature. METHODS: A prospective hospital study was carried out in 384 children with DEE, who underwent genetic testing. Metabolic disorders were evaluated with biochemical blood/urine assays and when required CSF estimations performed. RESULTS: A total of 154 pathogenic/likely pathogenic variants in 384 children were identified. Out of 384 children, 89 were clinically suspected to have probable or possible metabolic disorders. Pathogenic/likely pathogenic variants in metabolic genes were identified in 39 out of 89 (43.8 %) and promising VUS in 28 (31.4 %). These included variants for progressive myoclonus epilepsies (21; 53.8 %), DEE with focal/multifocal seizures (8; 20.5 %), generalized epilepsy (5;12.8 %), early myoclonic encephalopathy (2; 5.1 %), LGS (1; 2.6 %) and West syndrome (2; 5.1 %). CONCLUSION: Our cohort demonstrates for the first time from the Indian subcontinent that identification of metabolic variants can guide investigations and has therapeutic implications in patients with variable DEE phenotypes. A high utility is noted with regard to diagnosis and prognostication, given the low yield of available biochemical tests, indicating cost-effectiveness of this approach.

The effect of curcuma longa extract and significance of mordant as an alternative for eosin in H and E: A comparative study.

Background and Aim: Hematoxylin and Eosin (H and E) staining is a common and routine staining method used in Histopathology. In origin, Hematoxylin is natural and Eosin is a synthetic dye. Synthetic dyes are widely accepted due to its staining efficiency. However, due to synthetic and toxic properties, natural alternatives have gained importance. In this present study, Curcuma Longa rhizome (Turmeric) extract with and without mordant are examined as a natural substitute for Eosin in H and E staining. This study assessed the staining quality of Turmeric (H and T) compared to Eosin (H and E) and the significance of mordant in H and T staining. Materials and Methods: A comparative study is conducted in a Histopathology laboratory in a tertiary care hospital. Five tissue specimens were collected and stained with H and T with mordant, H and T without mordant, and conventional H and E stain. Two independent pathologists examined the quality of each stain. The results are graded as excellent, good, and poor. These results are statistically compared and analyzed. Result: Staining quality of Turmeric and Eosin are comparable to each other. At the same time, Turmeric gives yellow color instead of pink in Eosin. The result also shows that the addition of mordant in Turmeric significantly improves the staining quality. Interpretation and Conclusion: Turmeric with mordant can be used as an alternative stain to synthetic Eosin in H and E staining.

GC-MS analysis and in silico docking of constituents of Cinnamomum malabatrum against CYP450 17α and CYP450 19 (Aromatase)- Key targets for hyperandrogenism.

Poly cystic ovary syndrome (PCOS) is considered as one of the common hormonal disorders affecting 6-20% of women in their reproductive age with characteristic features include anovulatory infertility, hyperandrogenism, cystic follicles and insulin resistance. The gene CYP play an important role in pathophysiology of hyperandrogenism associated with PCOS. An elevated androgens are reported in PCOS condition due to overexpression of the enzyme CYP450 17 α: . As well as diminished levels of aromatase (CYP450 19) were observed in several hyperandrogenic PCOS patients. The powdered leafy material of Cinnamomum malabatrum was subjected to Soxhlet extraction. The plant extract was subjected to Gas chromatography-MS analysis (GC-MS), and the chromatogram obtained revealed the presence of active chemical constituents like 1(10),9(11)-B-Homolanistadiene for the first time and other potential compounds. Hypothesis has raised to interpret the efficiency of phytoconstituents of Cinnamomum malabatrum on these enzyme targets and which may be a novel drug candidate for the treatment and maintenance of hyperandrogenism associated with PCOS. Thus, the results obtained from the in-silico study of Cinnamomum malabatrum leaf extract using computational approaches indicate that the phytoconstituents have good affinities for the selected two key targets. ADME and PASS studies has been performed for active phytoconstituents homolanistadiene, ß-sitosterol, cycloartenol and a pyrazole derivative, and results revealed the Lipinski drug-likeness and pharmacological potential. In conclusion, this work throws a new insight into the possibility of the active phytoconstituents on binding the two active CYP45017 α and CYP45019 aromatase enzymes which facilitates development of novel compounds for hyperandrogenism associated with PCOS.

Insilico generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CLpro) using deep learning.

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski's rule of 5, high binding affinity (highest binding affinity: -9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19.

Vitamin D and its association with severity and control of childhood bronchial asthma.

Background: Bronchial asthma is a common disease in childhood. Vitamin D deficiency is a common unidentified nutritional deficiency. In spite of high prevalence, an association between the two has not been well understood. Objectives: Our study aimed to determine serum Vitamin D levels among asthmatic children and its association with clinical severity and level of control. Methods: A hospital-based cross-sectional study was conducted from 2017 to 2019 where 64 recurrent wheezers, classified into 6-15 years and the under 5 wheezers as per Global Initiative for Asthma guidelines, were included. The group of asthmatic children was comparable with respect to their demographic profiles with good adherence and proper inhaler use. Serum Vitamin D levels were estimated using an enzyme-linked immunosorbent assay and classified using the US Endocrine Society classification. Association between Vitamin D status and outcome variables was analyzed using Chi-square test, Fisher's exact test, unpaired t-test, and ANOVA. Results: Among the 64 wheezers, 29 (45.3%) had intermittent symptoms and 35 (54.7%) had persistent symptoms. Mean Vitamin D levels in the entire study population were in deficiency range (18.96 ng/ml ± 2.23). Persistent asthmatics had significantly lower Vitamin D levels (13.75 ng/ml) as compared to intermittent asthmatics (28.52 ng/ml). Those asthmatics who had hypovitaminosis D had higher rates of hospitalization (P = 0.048), increased use of rescue medications (P = 0.008), and poor symptom control (P = 0.001). Conclusions: Asthmatic children had a higher incidence of reduced Vitamin D levels showing a statistically significant association. There is also a significant association between Vitamin D level and poor symptom control, hospitalization for exacerbations, and requirement of rescue medication in asthmatic children.

Satisfaction among persons with epilepsy towards physical consultation versus online video consultation for follow-up.

PURPOSE: Telemedicine gained popularity in the setting of the COVID-19 pandemic. We aimed to study the satisfaction levels of persons with epilepsy (PWE) with online video consultation (OVC) and physical consultation (PC). METHODS: This was a cross-sectional questionnaire-based study conducted in a tertiary referral care center for epilepsy in India. All PWE who had availed of both OVC and PC were included. Those who did not give consent to a questionnaire were excluded. A questionnaire was given to assess patients' satisfaction regarding OVC and PC. Scores for each question for both OVC and PC were compared. RESULTS: One hundred and forty-one patients who had PC earlier and later availed of OVC from December 2020 to July 2021 formed the cohort. Seventy one patients who responded to the questionnaire were included. 49% and 51% of the patients belonged to urban and rural regions respectively. 8.5% of the patients were off anti-seizure medications (ASM), while 5.6% and 85.9% were on single and multiple ASMs respectively. There were no differences between PC and OVC regarding ease of getting the appointment, privacy during a consultation, patients' perceived chances of missing consultations, and overall comfort and experience on either type of consultation. Physical consultation scored more than OVC in patients' satisfaction with the time doctor spent with them, an opportunity to communicate their queries well, clarifications received from the doctor, and the likelihood of patients recommending the particular type of consultation to others(p < 0.05). CONCLUSIONS: Online video consultation can be a satisfactory alternative to PC and can improve patient satisfaction if some of the issues in OVC are addressed properly.

Potential of Catharanthus roseus applied to remediation of disparate industrial soils owing to accumulation and translocation of metals into plant parts.

Soil pollution is one of the major environmental concerns. Since the inception of the industrial revolution, numerous perilous compounds are being introduced into the environment by various means. Of these, heavy metals are considered the important soil contaminants that present significant peril to human health. While the preventive measures of environmental pollution lie in the awareness of mankind, eliminating the interfering consequences of pollutants that have already been released into the environment is the current challenge. The present work, therefore, aimed to determine the phytoremediation potential of Catharanthus roseus based on contamination indices. The metal concentrations in soil and plant were assessed using Atomic Absorption Spectrophotometry and Inductively Coupled Plasma -Mass Spectrophotometry. The results showed that C. roseus acted as a good tool in remediating industrially contaminated soils. Plants grown under metal stress showed enhanced antioxidant potential. Further, the plant exhibited increased chlorophyll, pectin and lignin content in response to heavy metals, suggesting significant relation between plant metabolism and mental stress. Phytoremediation using plants like C. roseus therefore, can be esthetically pleasing and more publicly acceptable than the disruptive physical and chemical processes currently in use.

The present study was undertaken for the first time to evaluate the potential of Catharanthus roseus to remediate the industrially contaminated soils of Visakhapatnam city. Plant responses to heavy metals were analyzed based on the alterations in antioxidant potential, lignin and pectin content of plants grown in these soils.

C12orf57 pathogenic variants: a unique cause of developmental encephalopathy in a south Indian child.

Open reading frame variants which lack stop codons such as C12orf57 variants are known to cause Temtamy syndrome, an extremely rare disorder characterized by intellectual disability, seizures, facial dysmorphism and agenesis of corpus callosum. C12orf57 was initially reported to be required for human corpus callosum development. We report the first child who is of Indian origin with developmental and epileptic encephalopathy (DEE) with a unique phenotypic evolution as focal onset reflex seizures. We performed whole exome sequencing of genomic DNA isolated from peripheral blood samples of proband and his parents. Two pathogenic compound heterozygous variants, a start loss variant (Chr12:7053285:c.1A>G) and a premature stop gain variant (Chr12:7053327:c.43C>T), involving the C12orf57 gene were identified in the proband. Our case report which details genotyping in this rare syndromic developmental encephalopathy, with no prior cases reported from India, expands the ethnic spectrum of patients.

Does Etiology and Hypsarrhythmia Subtype Influence Outcome in West Syndrome? Challenges Encountered from a Referral Center Perspective.

Background: Prediction of outcome of West syndrome (WS) in relation to etiology and electrophysiology remain pertinent challenges. Objective: This study aimed to compare electro-clinical and imaging characteristics between WS of "unknown-etiology"; "symptomatic"WS; to gauge the evolution and impact of electroencephalographic (EEG) patterns on seizure outcomes. Materials and Methods: Electro-clinico-radiological data of 76 children with WS who were followed up for atleast 1 year was collected for reviewing clinical, therapeutic and EEG profiles (sub-typed as typical and modified hypsarrhythmia [HA]). Quantified seizure scores were assessed. Results: Among 76 children included in this retrospective analysis, 31 (40.8%) were of unknown-etiology and 45 (59.2%) were "symptomatic" (structural cause/developmental-encephalopathy). Children with symptomatic WS (p = 0.037), specifically with gliosis on imaging (p = 0.05) and typical HA (including the multifocal subtype; P = 0.023) were more likely to have other seizure types before onset of spasms and exhibit prior delay or regression in milestones (p = 0.017). There was negative correlation between time to diagnosis and reduction in seizure scores (r = -0.32; p = 0.005).Significant reduction was noted in seizure scores with pharmacotherapy, irrespective of etiology (P < 0.001 in unknown-etiology and symptomatic subgroups). Seizure freedom rates did not differ between typical and modified HA groups (p = 0.215) with a higher proportion of children with meaningful reduction in seizure scores in the former sub-group (p = 0.030). Children who failed to achieve seizure remission were more likely to exhibit developmental impairment (p = 0.019). Conclusions: Early diagnosis and initiation of optimal therapy is crucial towards improving outcome, irrespective of etiology (which impacts pre-spasm development) and HA subtypes.

Clinical outcomes of del nido cardioplegia and st thomas blood cardioplegia in neonatal congenital heart surgery.

OBJECTIVES: Cardioplegia is essential for adequate myocardial protection. There continues to remain ambiguity regarding the ideal cardioplegia for adequate myocardial protection in congenital heart surgery. This study compares clinical outcomes using St Thomas II solution and Del Nido cardioplegia in neonates undergoing cardiac surgery. METHODS: All neonates (<30 days) from 2011 to 2017 who underwent surgery requiring cardioplegic arrest were analyzed retrospectively. We divided the cohort into two groups depending on cardioplegia received, as group A (Blood cardioplegia with St Thomas II solution, n = 56) and group B (Del Nido cardioplegia, n = 48). Various demographic, intraoperative, early postoperative, and discharge variables were analyzed. RESULTS: Two groups were similar in age, gender, pre-operative diagnosis, and risk category. Cardiopulmonary bypass (CPB) time (P = 0.002), aortic cross-clamp (ACC) time (P = 0.018), and the number of doses of cardioplegia (P < 0.001) were significantly lower with Del Nido group. Though vasoactive inotropic score (VIS) (P = 0.036) was high during the first 24 h in the immediate postoperative period in group A, there was no difference in early mortality among both groups (P = 0.749). Both groups did not show significant differences related to various postoperative and discharge variables. CONCLUSION: When compared to St. Thomas solution, the use of Del Nido cardioplegia solution in neonates is associated with a significant decrease in CPB and ACC times and VIS in the first 24 h after surgery. The choice of cardioplegia (St Thomas/Del Nido) in neonates does not affect early mortality and early postoperative clinical outcomes.