Association of polymorphism in the promotor area of the caprine BMPR1B gene with litter size and body measurement traits in Damani goats.

This study aimed to explore polymorphisms in the promoter region of the caprine BMPR1B (Bone morphogenetic protein receptor 1 beta) gene and its association with body measurement and litter size traits in Damani does. A total of 53 blood samples were collected to analyze the association between the BMPR1B gene polymorphism and 11 phenotypic traits in Damani female goats. The results revealed that three novel SNPs were identified in the promoter region of the caprine BMPR1B gene, including g.67 A > C (SNP1), g.170 G > A(SNP2), and g.501A > T (SNP3), among which the SNP1 and SNP2 were significantly (p < 0.05) associated with litter size and body measurement traits in Damani goats. In SNP1 the AC genotype could be used as a marker for litter size, and the CC genotype for body weight in Damani goats. In SNP2, the genotype GG was significantly (p < 0.05) associated with ear and head length. Therefore, we can conclude from the present study, that genetic variants AC and CC of the caprine BMPR1B gene could be used as genetic markers for economic traits through marker-assisted selection for the breed improvement program of the Damani goat.

Oral mucositis & oral health related quality of life in women undergoing chemotherapy for breast cancer in Karachi, Pakistan: A multicenter hospital based cross-sectional study.

BACKGROUND: Oral mucositis is an inflammatory condition of oral cavity which is a common and serious side effect of cancer treatment. Severe oral mucositis compromises basic functions like eating and swallowing causing malnutrition also affecting overall patient's oral health related quality of life. The aim of the study was to find the frequency of oral mucositis in patients with breast cancer during their chemotherapy, the factors associated with oral mucositis & the overall patient's oral health related quality of life. METHODS: A cross-sectional study was conducted and a total of 160 women diagnosed with breast cancer, receiving chemotherapy and who had undergone at least one cycle of chemotherapy were recruited from two hospital settings. In-person interviews were done, patients were asked questions about their sociodemographic history, personal habits, oral history and oral findings, breast cancer stage, chemotherapy history and Oral Health Related Quality of Life. Their oral examination was done at the end of the interview to assess presence or absence of oral mucositis, using World Health Organization oral mucositis tool. Oral Health Related Quality of Life was assessed using Oral Health Impact Profile-14 questionnaire. RESULTS: Our results showed that out of 160 patients 88 (55%) of the breast cancer cases developed oral mucositis during chemotherapy. The mean Oral Health Impact Profile -14 scores in patients with oral mucositis was high 18.36±0.96 showing poor Oral Health Related Quality of Life. Occasional frequency of brushing was significantly associated with oral mucositis (Prevalence ratio:2.26, 95%_CI 1.06-4.84) compared to those patients who brushed once and twice daily. Low level of education showed negative association with oral mucositis (Prevalence ratio:0.52, 95%_CI 0.31-0.88). CONCLUSION: Our study showed significant positive association of occasional brushing with OM and protective association of low level of education with the development of OM. Emphasis should be given to oral hygiene instructions and dental education to cancer patients in oncology clinics with the prescription of mouth washes, gels and toothpaste to patients to decrease OM during chemotherapy.

Understanding the Landscape of Bronchoscopy in Lung Cancer: Insights From Lesion Location, Gender, and Diagnostic Efficacy.

INTRODUCTION: Lung cancer constitutes a critical global health concern. According to the International Agency for Research on Cancer's (IARC) GLOBOCAN 2020 estimates, lung cancer is the leading cause of death in cancer patients. In areas where tuberculosis is prevalent, misdiagnosis and mistreatment frequently result from overlap, creating significant difficulties that delay diagnosis and treatment. Amid this complication, bronchoscopic techniques emerge as critical diagnostic tools, though their efficacy varies between studies. METHOD: Our retrospective study, conducted from July 2021 to December 2022 at the Department of Respiratory Medicine, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, examined 156 participants with malignancies. Our focus encompassed diverse lesions within the bronchial landscape, revealing intriguing findings. RESULTS: Bronchoscopic examinations unravelled prevalent abnormalities: 52 (33.3%) manifested as intraluminal growth, 48 (31.6%) as mucosal irregularities, and a less frequent (16, 10.3%) as an intraluminal bulge. Transbronchial needle aspiration stood out with a 10/11 (91%) positivity rate, biopsy came in second at 38/46 (83%), and bronchoalveolar lavage showed a 44/152 (29%) positivity rate. It was interesting to see how the lesions were spread out among the different types of histology. For example, squamous cell carcinoma showed 17/37 (46%) intraluminal growth, while adenocarcinoma showed 22/60 (36.7%) intraluminal growth and 4/60 (6.7%) intraluminal bulge. Moreover, a significant absence of abnormalities was observed in various lesions, underlining the intricacies of characterising bronchial lesions. CONCLUSION: Our study shows that direct tissue sampling is better and that new bronchoscopic technologies are important for diagnosing lesions that were hard to get to in the past. However, limitations in patient selection biases and the single-centre focus caution against generalised interpretations. Our research illuminates the pivotal role of bronchoscopic methods in diagnosing lung lesions, emphasising the necessity for continued advancements to enhance diagnostic accuracy and treatment efficacy in lung cancer subtypes.

Biochemical and computational inhibition of α-glucosidase by novel metronidazole-linked 1H-1,2,3-triazole and carboxylate moieties: kinetics and dynamic investigations.

In the current study, metronidazole derivatives containing 1H-1,2,3-triazole and carboxylate moieties were evaluated in vitro and by computational methods for their anti-diabetic potential to insight into their medicinal use for the management of type II diabetes mellitus. Interestingly all 14 compounds displayed high to significant inhibitory capability against the key carbohydrate's digestive enzyme α-glucosidase with IC50 values in range of 9.73-56.39 µM, as compared to marketed drug acarbose (IC50 = 873.34 ± 1.67 µM). Compounds 5i and 7c exhibited the highest inhibition, therefore, these two compounds were further evaluated for their mechanistic studies to explore its type of inhibition. Compounds 5i and 7c both displayed a concentration-dependent (competitive type of inhibition) with Ki values 7.14 ± 0.01, 6.15 ± 0.02 µM, respectively, which conclude their favourable interactions with the active site residues of the α-glucosidase. Interestingly all compounds are non-cytotoxic against BJ cell line. To further validate our findings, in-silico approaches like molecular docking, and molecular dynamic simulations were applied to investigate the mode of bindings of compounds with the enzyme and identifies their inhibition mechanism, which strongly complements our experimental findings.Communicated by Ramaswamy H. Sarma.

Comparing redo surgery and stereotactic radiosurgery for recurrent, residual, and/or tumors showing progression in nonfunctioning pituitary adenomas: A systematic review and meta-analysis.

Background: Non-functioning pituitary adenomas (NFPAs) are well-differentiated benign tumors originating from the adenohypophyseal cells of the pituitary gland. They present with headaches, visual disorders, or cranial nerve deficits. NFPAs can recur, progress, or present as residual tumors. We, therefore, conducted this review to compare the effects of both revision surgery and stereotactic surgery on tumor size, visual status, endocrine status, and complications. Methods: A systematic review of published literature on recurrent, residual, or progressing NFPAs that underwent redo surgery or stereotactic radiosurgery from the inception till June 2020 was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirteen records (1209 patients) were included, and risk ratio (RR) and 95% confidence intervals (CIs) estimated from each study were pooled using a random-effects meta-analysis model. Results: Redo surgery was the preferred intervention in patients presenting with larger tumor sizes and was more effective in reducing the tumor size as compared to stereotactic radiosurgery (SRS) (risk ratio [RR] 56.14; 95% CI, 16.45-191.58). There was more visual loss with revision surgery as compared to SRS (risk ratio [RR] 0.08; 95% CI, 0.03-0.20). However, SRS was associated with fewer complications, such as new diabetes insipidus, as compared to the redo surgery (risk ratio [RR] 0.01; 95% CI 0.01-0.03). Conclusion: Redo surgery is the superior choice in the treatment of recurrent/residual or progressing NFPAs if the tumor size is large and an immediate reduction in tumor burden through debulking is warranted. However, redo surgery is associated with a higher risk of visual loss, new endocrinopathies, and other complications, in contrast to SRS.

Sakuranetin ameliorates streptozotocin-induced diabetes in rodents by inhibiting caspase-3 activity, modulating hematological parameters, and suppressing inflammatory cytokines: a molecular docking and dynamics study.

Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1ß (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.Communicated by Ramaswamy H. Sarma.

Frequency of Contamination on Used Healing Abutments after Sterilization: An In Vitro Study.

PURPOSE: To determine and compare the frequency of contamination on different sites of healing abutments (HAs) after sterilization with Phloxine B dye on unused and used HAs after sterilization. MATERIALS AND METHODS: A total of 60 HAs were divided into two test groups: (1) used and sterilized and (2) a control group (unused). The test group was evaluated for contamination after sterilization; the control group did not undergo any procedure. Data were analyzed using SPSS version 22 (IBM). Descriptive statistics were used to determine the frequency of contamination in the different groups and at the different HA sites. Chi-square test was used to evaluate the association of frequency of contamination with the HA site and design. The level of significance was kept at P ≤ .01. RESULTS: The test group showed more contamination compared to the control group. The most contaminated sites were the screw thread and the screwdriver engagement location. CONCLUSIONS: HA reuse is cost-effective, but cleaning and sterilization was not effective for these components; thus, HAs need to be reused with caution because they were heavily contaminated when compared to new HAs. Among the different sites, the screw thread and screwdriver engagement sites were more prone to contamination. HA type did not influence the frequency of contamination.

The emerging role of noncoding RNAs in the PI3K/AKT/mTOR signalling pathway in breast cancer.

Breast cancer persists as a major problem for the world's healthcare, thus it is essential to fully understand the complex molecular processes that cause its growth and development. ncRNAs had been discovered to serve critical roles in a variety of cellular functions, including the regulation of signalling pathways. Within different pathways, the AKT/PI3K/mTOR signalling cascade has received a lot of interest because of its role in cancer. A complex interaction between ncRNAs, notably miRNAs, lncRNAs, and circRNAs, and the AKT/PI3K/mTOR signalling pathway exerts both oncogenic and tumor-suppressive activities by targeting critical components of the pathway directly or indirectly. Through miRNA-mediated post-transcriptional regulation, lncRNA-guided chromatin remodelling, and circRNA sequestration, ncRNAs modulate the activity of PI3K, AKT, and mTOR, influencing cell proliferation, survival, and metastasis. Furthermore, ncRNAs can serve as promising biomarkers for breast cancer prognosis, diagnosis, and treatment response, as their dysregulation is commonly observed in breast cancer patients. Harnessing the potential of ncRNAs as therapeutic targets or tools for restoring pathway homeostasis holds promise for innovative treatment strategies in breast cancer. Understanding the intricate regulatory networks orchestrated by ncRNAs in this context may pave the way for novel diagnostic approaches, therapeutic interventions, and a deeper comprehension of breast cancer's molecular landscape, ultimately improving patient outcomes. This abstract underscores the emerging significance of ncRNAs in the AKT/PI3K/mTOR signaling pathway in breast cancer.

Insights from international environmental legislation and protocols for the global plastic treaty.

Plastic pollution has emerged as a global challenge necessitating collective efforts to mitigate its adverse environmental consequences. International negotiations are currently underway to establish a global plastic treaty. Emphasizing the need for solution-orientated research, rather than focusing on further defining the problems of widespread environmental occurrence and ecological impacts, this paper extracts insights and draws key patterns that are relevant for these international negotiations. The analysis reveals that (i) environmental rather than human health concerns have been the predominant driving force behind previous regulations targeting pollutants, and (ii) the decision to ban or discontinue the use of harmful pollutants is primarily affected by the availability of viable substitutes. These two key findings are relevant to the discussions of the ongoing Intergovernmental Negotiating Committee (INC) on the global plastic treaty and underscore the recognition of environmental consequences associated with plastic pollution while emphasizing the need to enhance the knowledge base of potential human health risks. Leveraging the availability of substitutes can significantly contribute to the development and implementation of effective strategies aimed at reducing plastic usage and corresponding pollution.

Impact of fixed dental prosthesis on neuroimaging: assessment of artefacts.

Objectives: To determine the frequency and extent of artefacts in magnetic resonance imaging and/or computed tomography scans of head caused by fixed dental prosthesis. METHODS: The retrospective study was conducted at Aga Khan University Hospital from July to December 2021, and comprised magnetic resonance imaging and/or computed tomography scans from January 2015 to December 2020 of the head of individuals with existing fixed dental prosthetic work at the time of exposure. They were analysed for the presence of artefacts. The association between artefacts and the presence of fixed dental prosthesis was explored. Data was analysed using SPSS 23. RESULTS: Of the 297 images evaluated, 173 (58%) were magnetic resonance imaging scans, and 124(42%) were computed tomography scans. The most common artefacts was grade I 148(49.8%), followed by grade II 140(47.1%) and grade III 9(3%). There was no significant association between fixed dental prosthesis and the artefacts (p>0.05). Conclusion: There should be no reservations in placing fixed metal prosthesis in individuals on account of future brain scans.

Does the sagittal root position of maxillary anterior teeth affect the decision making on immediate implants in the anterior maxilla? A CBCT-based study.

BACKGROUND: Immediate implant placement in the maxillary esthetic zone is a challenging and demanding task. To achieve favorable results, proper case selection and treatment planning are necessary. Variables like the sagittal root position (SRP) and the labial bone thickness (LBT) of maxillary anterior teeth are of paramount importance for predictable outcomes. OBJECTIVES: The aim of the present study was to evaluate the SRP and LBT of maxillary anterior teeth in the context of immediate implant placement by using cone-beam computed tomography (CBCT) in a sample of the Pakistani population. MATERIAL AND METHODS: A cross-sectional study was conducted using the CBCT scans of patients. The SRP of each tooth (maxillary canine to canine) was evaluated in the sagittal section of a CBCT scan according to the classification by Kan et al. The LBT of each tooth was measured perpendicularly to the long axis of tooth at 3 sites: at the alveolar crest (P1); 2 mm from the alveolar crest (P2); and 4 mm from the alveolar crest (P3). Descriptive statistics were reported for SRP and LBT. The χ2 test was employed to assess any association between the variables. RESULTS: Class I SRP was the most prevalent (n = 196, 81.7%), while Class III was the least frequent (n = 1, 0.4%). The association between the tooth type and SRP was statistically non-significant (p = 0.510). CONCLUSIONS: In the evaluated sample of the Pakistani population, the most frequent type of the SRP of maxillary anterior teeth was Class I, which is most favorable for immediate implant placement. Furthermore, the labial bone in the maxillary esthetic zone was found to be mostly thin - LBT was within the range of 0.5-0.9 mm - which makes immediate implant placement in the anterior maxilla a challenge. The results of the present study could serve as a guide for clinicians in terms of appropriate patient selection for immediate implant placement in the maxillary esthetic zone.

Structural and energetic analysis of NS5 protein inhibition by small molecules in Japanese encephalitis virus using machine learning and steered molecular dynamics approach.

One of the viral diseases that affect millions of people around the world, particularly in developing countries, is Japanese encephalitis (JE). In this study, the conserved protein of this virus, that is, non-structural protein 5 (NS5), was used as a target protein for this study, and a compound library of 749 antiviral molecules was screened against NS5. The current study employed machine learning-based virtual screening combined with molecular docking. Here, three hits (24360, 123519051 and 213039) had lower binding energies (< -8 kcal/mol) than the control, S-Adenosyl-L-homocysteine (SAH). All the compounds showed significant H-bond interactions with functional residues, which were also observed by the control. Molecular dynamics simulation, MM/GBSA for binding free energy analysis, principal component analysis and free energy landscape were also performed to study the stability of the complex formation. All three compounds had similar root mean square deviation trends, which were comparable to the control, SAH. Post-MD, the 123519051-receptor complex had the highest number of H-bonds (4 to 5) after the control, out of which three exhibited the highest percentage occupancy (50%, 24% and 79%). Both docking and MD, 123519051 showed an H-bond with the residue Gly111, which was also found for the control-protein complex. 123519051 showed the lowest binding free energy with ΔGbind of -89 kJ/mol. Steered molecular dynamics depicted that 123519051 had the maximum magnitude of dissociation (1436.43 kJ/mol/nm), which was more than the control, validating its stable complex formation. This study concluded that 123519051 is a binder and could inhibit the protein NS5 of JE.Communicated by Ramaswamy H. Sarma.

In silico assessment of a natural small molecule as an inhibitor of programmed death ligand 1 for cancer immunotherapy: a computational approach.

Programmed cell death ligand 1 (PD-L1) is a crucial target for cancer therapy. Here, an in silico study investigates PD-L1 to inhibit its interaction with PD1, thereby promoting an immune response to eliminate cancer cells. The study employed machine learning (ML) -based QSAR to detect PDL1 inhibitors. Morgan's fingerprint with docking score showed a 0.83 correlation with the experimental IC50, enabling the screening of 3200 natural compounds. The top three compounds, considered 2819, 2821 and 3188, were selected from the ML-based QSAR and subjected to molecular docking and simulation. The binding scores for 2819, 2821 and 3188 were -7.0, -9.0 and -8.9 kcal/mol, respectively. The stability of the ligands during a 100 ns simulation was assessed using RMSD, showing that 2819 and 2821 maintained stable patterns comparable to the control inhibitor. Notably, 2819 exhibited a consistent stable pattern throughout the simulation, while 2821 showed stability in the last 40 ns. The control compound showed the highest number of hydrogen bonds with proteins, whereas compounds 2819 and 2821 formed continuous H-bonds. 3188 was separated from the protein in later phases and is not regarded as a potential PD-L1-binding molecule. MMGBSA binding free energy for complexes was computed. Control had the lowest binding free energy, while 2819 and 2821 also had lower binding energies. In contrast, 3188 showed poor binding free energy, causing protein separation. Principal component analysis showed a loss of entropy and reduced protein conformational variation. Overall, 2819 and 2821 are potential binders for PD-L1 inhibition and immune response triggering.Communicated by Ramaswamy H. Sarma.

Oral health related quality of life in head and neck cancer survivors within the first year following treatment: a cross-sectional study in Karachi, Pakistan.

After completing treatment for head and neck cancer (HNC), patients often face oral complications like oral pain, limited mouth opening and dry mouth which significantly reduce their oral health related quality of life (OHRQoL). These issues impact their overall well-being, social activities and long-term survival. The primary objective of this study was to evaluate OHRQoL and its association with sociodemographic characteristics, oral hygiene practices and oral clinical parameters such as oral hygiene status and oral mucositis grade in patients who have completed treatment for head and neck cancer. This cross-sectional study involved 79 HNC-treated patients within first year after completion of cancer treatment attending ENT and dental clinics at outpatient department (OPD) setting in Karachi. Data was collected electronically using structured questionnaire comprising of EORTC QLQ H&N - 35 to measure OHRQoL, patients were also examined for oral hygiene status using oral hygiene index- simplified (OHI-s) and oral mucositis grade using WHO oral mucositis scale. Multiple linear regression was used to test OHRQoL associations with the sociodemographic and different clinical factors. The result showed an overall mean score for oral health related quality of life (OHRQoL) of 25.02 ± 15.86 (95% CI 21.46-28.57), with difficulty in mouth opening 53.16 ± 18.88 and dry mouth 45.14 ± 24.48 being predominant concerns for decline in the OHRQoL in the population. Male predilection was observed among participants n = 60 (75.9%), majority of the participants n = 41 (51.9%) were below 52 years of age. n = 63 (80%) participants received radiotherapy alongside surgery and chemotherapy. Most of participants n = 66 (83.5%) experienced moderate to severe oral mucositis with poor oral hygiene status n = 56 (71%). Significant associations were found between OHRQoL and BMI, OH status, marital status, monthly income, gender and fluoride toothpaste (p < 0.05). These findings suggest that Quality of Life (QoL) among HNC treated patients is negatively impacted by their poor oral health, post cancer treatment. Therefore, it is important to evaluate and modify the current treatment modalities and involve multidisciplinary teams, to improve their OHRQoL thereby enhancing overall QoL.

From diagnosis to therapy: The transformative role of lncRNAs in eye cancer management.

The genomic era has brought about a transformative shift in our comprehension of cancer, unveiling the intricate molecular landscape underlying disease development. Eye cancers (ECs), encompassing diverse malignancies affecting ocular tissues, pose distinctive challenges in diagnosis and management. Long non-coding RNAs (lncRNAs), an emerging category of non-coding RNAs, are pivotal actors in the genomic intricacies of eye cancers. LncRNAs have garnered recognition for their multifaceted roles in gene expression regulation and influence on many cellular processes. Many studies support that the lncRNAs have a role in developing various cancers. Recent investigations have pinpointed specific lncRNAs associated with ECs, including retinoblastoma and uveal melanoma. These lncRNAs exert control over critical pathways governing tumor initiation, progression, and metastasis, endowing them with the ability to function as evaluation, predictive, and therapeutic indicators. The article aims to synthesize the existing information concerning the functions of lncRNAs in ECs, elucidating their regulatory mechanisms and clinical significance. By delving into the lncRNAs' expanding relevance in the modulation of oncogenic and tumor-suppressive networks, we gain a deeper understanding of the molecular complexities intrinsic to these diseases. In our exploration of the genomic intricacies of ECs, lncRNAs introduce a fresh perspective, providing an opportunity to function as clinical and therapeutic indicators, and they also have therapeutic benefits that show promise for advancing the treatment of ECs. This comprehensive review bridges the intricate relationship between lncRNAs and ECs within the context of the genomic era.

Computational insights into overcoming resistance mechanisms in targeted therapies for advanced breast cancer: focus on EGFR and HER2 co-inhibition.

In the present study, the formation of a heterodimer involving both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) has been explored as a potential therapeutic mechanism to inhibit the progression of breast cancer. Virtual screening using molecular docking resulted in the three hit compounds (ZINC08382411, ZINC08382438, and ZINC08382292) with minimum binding scores and commonly binding to both receptors. Further, MD simulation analysis of these complexes illustrated the high stability of these compounds with EGFR and HER2. RMSD showed that ZINC08382411 displayed the most stable RMSD of 2 - 3 Å when bound to both receptors, suggesting to have strong compatibility with the active site of the receptor. Hydrogen bond analysis showed that ZINC08382411 forms the maximum number of H-bonds (2 to 3) in both EGFR and HER2 bound complexes, with the highest occupancy of 62% and 79%, respectively. Binding free energy calculation showed that ZINC08382411 possesses maximum affinity towards both the receptors with ΔGbind = -129.628 and -164.063 kJ/mol, respectively. This approach recognizes the significance of EGFR and HER2 in breast cancer development and aims to disrupt their collaborative signaling, which is known to promote the antagonistic behavior of cancer cells. By focusing on this EGFR/HER2 heterodimer, the study offers a promising avenue for identifying a potential candidate (ZINC08382411) that may inhibit breast cancer cell growth and potentially improve patient outcomes. The study's findings may contribute to the ongoing efforts to advance breast cancer treatment strategies.Communicated by Ramaswamy H. Sarma.

Setting the boundaries and scope of practice for the two sister specialities of dentistry: Operative dentistry-endodontics and prosthodontics.

Dental academia in Pakistan has recently achieved an important milestone. The name of Operative Dentistry speciality has been changed to Operative Dentistry & Endodontics (ODE). It was a much-needed change that was first felt about two decades ago. However, with the correction of name, there are certain challenges that this speciality has to manage now. These include improving the curriculum, setting up standards, and lastly, setting up its boundaries and scope of practice as some of its scope overlaps with a sister speciality called Prosthodontics. This overlapping of the boundaries of dental disciplines is a problem that is unique to Pakistan, India, and some East Asian countries where Operative Dentistry or Conservative Dentistry is combined with Endodontics. This paper aims to discuss the objective delineation of dental procedures and suggest a model of peaceful co-existence of sister dental specialities.

Exploring the lncRNA-VEGF axis: Implications for cancer detection and therapy.

Cancer is a complicated illness that spreads indefinitely owing to epigenetic, genetic, and genomic alterations. Cancer cell multidrug susceptibility represents a severe barrier in cancer therapy. As a result, creating effective therapies requires a better knowledge of the mechanisms driving cancer development, progress, and resistance to medications. The human genome is predominantly made up of long non coding RNAs (lncRNAs), which are currently identified as critical moderators in a variety of biological functions. Recent research has found that changes in lncRNAs are closely related to cancer biology. The vascular endothelial growth factor (VEGF) signalling system is necessary for angiogenesis and vascular growth and has been related to an array of health illnesses, such as cancer. LncRNAs have been identified to alter a variety of cancer-related processes, notably the division of cells, movement, angiogenesis, and treatment sensitivity. Furthermore, lncRNAs may modulate immune suppression and are being investigated as possible indicators for early identification of cancer. Various lncRNAs have been associated with cancer development and advancement, serving as cancer-causing or suppressing genes. Several lncRNAs have been demonstrated through research to impact the VEGF cascade, resulting in changes in angiogenesis and tumor severity. For example, the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to foster the formation of oral squamous cell carcinoma and the epithelial-mesenchymal transition by stimulating the VEGF-A and Notch systems. Plasmacytoma variant translocation 1 (PVT1) promotes angiogenesis in non-small-cell lung cancer by affecting miR-29c and boosting the VEGF cascade. Furthermore, lncRNAs regulate VEGF production and angiogenesis by interacting with multiple downstream signalling networks, including Wnt, p53, and AKT systems. Identifying how lncRNAs engage with the VEGF cascade in cancer gives beneficial insights into tumor biology and possible treatment strategies. Exploring the complicated interaction between lncRNAs and the VEGF pathway certainly paves avenues for novel ways to detect better accurately, prognosis, and cure cancers. Future studies in this area could open avenues toward the creation of innovative cancer therapy regimens that enhance the lives of patients.

HOTAIR: A key regulator of the Wnt/ß-catenin signaling cascade in cancer progression and treatment.

The long non-coding RNA (lncRNA) HOTAIR occupies a central position in the complex domain of cancer biology, particularly concerning its intricate interplay with the Wnt/ß-catenin signaling pathway. This comprehensive review explores the multifaceted interactions between HOTAIR and the Wnt/ß-catenin cascade, elucidating their profound function in cancer growth, progression, and therapeutic strategies. The study commences by underscoring the pivotal role of the Wnt/ß-catenin cascade in governing essential cellular activities, emphasizing its dysregulation as a linchpin in cancer initiation and advancement. It introduces HOTAIR as a crucial regulatory entity, influencing gene expression in both healthy and diseased. The core of this review plunges into the intricacies of HOTAIR's engagement with Wnt/ß-catenin signaling. It unravels how HOTAIR, through epigenetic modifications and transcriptional control, exerts its influence over key pathway constituents, including ß-catenin, Wnt ligands, and target genes. This influence drives unchecked cancer cell growth, invasion, and metastasis. Furthermore, the review underscores the clinical significance of the HOTAIR-Wnt/ß-catenin interplay, elucidating its associations with diverse cancer subtypes, patient prognoses, and prospects as a therapy. It provides insights into ongoing research endeavors to develop HOTAIR-targeted treatments and initiatives to facilitate aberrant Wnt/ß-catenin activation. Concluding on a forward-looking note, the article accentuates the broader implications of HOTAIR's involvement in cancer biology, including its contributions to therapy resistance and metastatic dissemination. It underscores the importance of delving deeper into these intricate molecular relationships to pave the way for groundbreaking cancer treatment.