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Aim The aim of this study was to evaluate the effectiveness of 5% eutectic mixture of local anesthetics (EMLA) cream and 20% benzocaine gel in reduction of pain during rubber dam clamp placement in the treatment of non-carious cervical lesions (NCCLs). Methodology In this split-mouth single-blind randomized clinical trial, 50 adult participants were selected from the outpatient department. The test group was treated using 5% EMLA cream for three minutes, and visual analog scale (VAS) scores were recorded. The comparison group was treated using 20% benzocaine gel and procedure was repeated as that in the test group. After recording the VAS scores, NCCLs in both the groups were restored using composite restoration. Results In the included 50 participants, 70% were males, with an age group of 31-67 years. The mean VAS score at 3 minutes in EMLA group was significantly lower than that in benzocaine group. Conclusion Application of 5% EMLA cream for 3 minutes showed greater pain reduction during rubber dam clamp placement as compared to 20% benzocaine gel in adult patients with NCCLs.
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The level of bacterial adhesion and bacterial microleakage in four different materials utilised to seal the access passage of screw retained implant supported prosthesis (SRIP) is of interest to dentists. Four distinct categories were created from the samples on the basis of restorative materials used for sealing access passage in SRIP. Guttapercha and light cured acrylic resin were found to have comparatively low bacterial adhesion and bacterial microleakage in sealing accessory canals in screw retained implant supported prosthesis.
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Alcohol use disorder accounts for a growing worldwide health system concern. Alcohol causes damages to various organs, including intestine and liver, primarily involved in its absorption and metabolism. However, alcohol-related organ damage risk varies significantly among individuals, even when they report consuming comparable dosages of alcohol. Factor(s) that may modulate the risk of organ injuries from alcohol consumption could be responsible for inter-individual variations in susceptibility to alcohol-related organ damages. Accumulating evidence suggests disruptions in circadian rhythm can exacerbate alcohol-related organ damages. Here we investigated the interplay between alcohol, circadian rhythm, and key tissue cellular processes at baseline, after a regular and a shift in the light/dark cycle (LCD) in mice. Central/peripheral clock expression of core clock genes (CoClGs) was analyzed. We also studied circadian homeostasis of tissue cellular processes that are involved in damages from alcohol. These experiments reveal that alcohol affects the expression of CoClGs causing a central-peripheral dyssynchrony, amplified by shift in LCD. The observed circadian clock dyssynchrony was linked to circadian disorganization of key processes involved in the alcohol-related damages, particularly when alcohol was combined with LCD. These results offer insights into the mechanisms by which alcohol interacts with circadian rhythm disruption to promote organ injury.
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Objective: While some patients may require surgical treatment a lot of patients do recover on conservative treatment alone while the optimal treatment being unclear. The purpose of this study was to treat the PT-RCTs conservatively for a period of 6 months and to determine its clinical outcome, radiological outcome on MRI and the baseline clinical factors predictive of that outcome. Methodology: All patients with a partial tear of supraspinatus and/or infraspinatus on their 1st MRI and aged 18-80 years were eligible and 47 patients (22 males, 25 females) were enrolled. Patients were evaluated using a standardised format including clinical history, imaging, and ASES(American Shoulder and Elbow Surgeons) score. Patients underwent a course of physical therapy for a period of minimum of 6 months which was augmented with the use of analgesics and/or anti-inflammatory drugs, multivitamins and supplements which were patient specific. Patients were followed up at 3 months and 6 months, ASES score was calculated, and a follow-up MRI was done at 6 months to determine if their tear had healed, remained the same, or progressed. A patient that had a better ASES score at 6 months was tagged as "clinically improved". Radiologically, patients were considered treated "successfully" if the tear size was reduced or remained the same while some "failed" that had an increased size of tear. Result: Non-operatively treated patients demonstrated a mean ASES score of 63.45 ± 16.24 at the end of 6 months. Overall, 35 patients (74.5 %) had the same size, seven patients (14.9 %) demonstrated tear progression and 5 (10.6 %) patients showed a decrease in size of their tear on MRI done at 6 months. In the end, 30 (63.8 %) patients improved clinically and 40 (85.1 %) patients improved radiologically. Statistical analysis also showed that patients with their non-dominant side involved and with an atraumatic onset of their injury were more likely to improve clinically. Conclusion: Conservative treatment of PT-RCTs may lead to a successful clinical outcome but it may or may not reveal itself radiologically. ASES score is an effective tool to evaluate and manage various conditions of the shoulder and not just the rotator cuff. The baseline factors such as onset (traumatic versus atraumatic) and shoulder involved (dominant versus non-dominant) can predict the outcome of conservative treatment.
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Fungal infections account for more than 140 million cases of severe and life-threatening conditions each year, causing approximately 1.7 million deaths annually. Candida albicans and related species are the most common human fungal pathogens, causing both superficial (mucosal and cutaneous) and life-threatening invasive infections (candidemia) with a 40-75% mortality rate. Among many virulence factors of Candida albicans, morphological transition from yeast to hyphae, secretion of hydrolytic enzymes, and formation of biofilms are considered to be crucial for pathogenicity. However, the arsenals for the treatment against these pathogens are restricted to only a few classes of approved drugs, the efficacy of which is being compromised by host toxicity, fungistatic activity, and the emergence of drug resistance. In this study, we have described the development of a molecule, exhibiting excellent antifungal activity (MIC 8 µg/mL), by tailoring acidic sophorolipids with aryl alcohols via enzyme catalysis. This novel derivative, ASLdC3, is a surface-active compound that lowers the surface tension of the air-water interface up to 2-fold before reaching the critical micelle concentration of 25 µg/mL. ASLdC3 exhibits excellent antibiofilm properties against Candida albicans and other nonalbicans Candida species. The molecule primarily exhibits its antifungal activity by perturbing mitochondrial function through the alteration of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS). The ROS damages fungal cell membrane function and cell wall integrity, eventually leading to cell death. ASLdC3 was found to be nontoxic in in vitro assay and nonhemolytic. Besides, it does not cause toxicity in the C. elegans model. Our study provides a valuable foundation for the potential of acidic sophorolipid as a nontoxic, biodegradable precursor for the design and synthesis of novel molecules for use as antimicrobial drugs as well as for other clinical applications.
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Since 2019, Lumpy skin disease (LSD) has suddenly spread in many Asian countries, including India. LSD primarily occurs in cattle. However, recent LSD outbreaks in India have also revealed significant morbidity and production losses in buffaloes. This has raised concerns about the role of buffaloes in the epidemiology and transmission of LSD and necessitates the inclusion of buffaloes in the mass vaccination program for the prevention and control of the disease in the country. However, there is no significant data on the immune response in buffaloes following vaccination with the LSD vaccine. In this study, we evaluated antibody- and cell-mediated immune responses following vaccination with a newly developed live-attenuated LSD vaccine (Lumpi-ProVacInd). The detectable amount of anti-LSDV antibodies was observed at 1-2 months following vaccination, with a peak antibody titer at 3 months. Upon stimulation of the peripheral blood mononuclear cells (PBMCs) with the UV-inactivated LSDV antigen, there was a significant increase in CD8 + T cell counts in vaccinated animals as compared to the unvaccinated animals. Besides, vaccinated animals also showed a significant increase in IFN-γ levels upon antigenic stimulation of their PBMCs with LSDV antigen. In conclusion, the buffaloes also mount a potent antibody- and cell-mediated immune response following vaccination with Lumpi-ProVacInd.
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Búfalos , Dermatosis Nodular Contagiosa , Virus de la Dermatosis Nodular Contagiosa , Vacunas Atenuadas , Vacunas Virales , Animales , Búfalos/inmunología , Dermatosis Nodular Contagiosa/prevención & control , Dermatosis Nodular Contagiosa/inmunología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Virus de la Dermatosis Nodular Contagiosa/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunología , India , Inmunidad Celular , Anticuerpos Antivirales/sangre , Vacunación/veterinaria , Leucocitos Mononucleares/inmunología , FemeninoRESUMEN
Maharaji rice, an aromatic variety with medium slender grains, is traditionally cultivated in the central regions of India. This study aimed to identify the biochemical compounds responsible for Maharaji rice's distinctive fragrance and enhance its agro-morphological traits through mutation breeding. Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) analysis, forty major metabolites were identified which may be responsible for its characteristic aroma. The bioactive compounds included terpenes, flavonoids, and amino acids. Maharaji brown rice extract exhibited potent radical scavenging activity. Radiation-induced mutation breeding improved the agro-morphological traits and also triggered biochemical diversification in different mutants. Maharaji Mutant-2 exhibited improved aroma due to higher abundance of aromatic compounds, improved yield and morphological characters as compared to the parent. This study, for the first time identifies the compounds associated with the characteristic aroma of Maharaji rice. Global metabolomics may, therefore, expedite the selection of mutants with suitable aroma and desirable biological properties.
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The deterioration of mild steel in an acidic environment poses a significant challenge in various industries. The emergence of effective corrosion inhibitors has drawn attention to studies aimed at reducing the harmful consequences of corrosion. In this study, the corrosion inhibition efficiency of Prinivil in a 1M HCl solution through various electrochemical and gravimetric techniques has been investigated for the first time. The results demonstrated that the inhibition efficiency of Prinivil expanded from 61.37% at 50 ppm to 97.35% at 500 ppm concentration at 298 K. With a regression coefficient (R 2) of 0.987, Kads value of 0.935 and Ea value of 43.024 kJ/mol at 500 ppm concentration of inhibitor, a strong affinity of Prinivil for adsorption onto the metal surface has been significantly found. Scanning electron microscopy (SEM) and contact angle measurement analyses further support the inhibitory behavior of Prinivil, demonstrating the production of a defensive layer on the surface of mild steel. Additionally, molecular dynamics (MD) and Monte Carlo simulations were employed to investigate the stability and interactions between Prinivil and the metallic surface (Fe (1 1 0)) at the atomic level. The computed results reveal strong adsorption of Prinivil upon the steel surface, confirming its viability as a corrosion inhibitor.
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Introduction. Timely and accurate diagnosis of diseases is crucial for effective patient care. Turnaround time (TAT) in surgical pathology, defined as the time between accessioning the sample and reporting results, is a key performance indicator reflecting quality and efficiency. This study explores factors affecting TAT for diagnostic biopsies in a tertiary oncology hospital. Methods. A 1-month pilot study was conducted, focusing on 695 in-house diagnostic biopsies. Biopsies were categorized as routine (requiring only hematoxylin and eosin (H&E) staining) or complex cases (requiring additional tests). TAT was defined as the time between sample accessioning and report availability in the electronic medical record, with delays defined as exceeding 3 days for routine cases and 4 days for complex cases. Survival analysis using Kaplan-Meier plots was utilized to analyze TAT. Results. The overall mean TAT was 3.7 ± 2 days, with routine cases at 3.1 ± 2 days and complex cases at 4.8 ± 2 days (P < 0.001). Survival analysis revealed prolonged TAT for complex cases. Organ-specific analysis highlighted variations in TAT, with brain biopsies presenting the highest complexity and longest TAT. Surprisingly, malignant cases demonstrated slightly shorter TATs compared to benign cases (P = 0.026). Delays were observed in 34% of all cases. Conclusions. Laboratory TAT is crucial and is frequently used as a performance benchmark. We analyzed the various causes of delayed TAT in our hospital's histopathology department, with an emphasis on variables in the analytical phase. The results of this study demonstrate that cases involving ancillary techniques had significantly longer TATs compared to routine H&E cases.
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This article describes the molecular mechanism by which tetraalkylammonium chloride ([R4N]Cl: R- = methyl (Me), ethyl (Et), propyl (Pr),butyl (Bu)) modulates the stability, folding, and dynamics of cytochrome c (Cyt c). Analysis of [R4N]Cl effects on thermal/chemical denaturations, millisecond refolding/unfolding kinetics, and slow CO-association kinetics of Cyt c without and with denaturant providing some significant results: (i) [R4N]Cl decreasing the unfolding free energy estimated by thermodynamic and kinetic analysis of thermal/chemical denaturation curves and kinetic chevrons (Log kobs-[GdmCl]) of Cyt c, respectively (ii) hydrophobicity of R-group of [R4N]Cl, preferential inclusion of [R4N]Cl at the protein surface, and destabilizing enthalpic attractive interactions of [Me4N]Cl and steric entropic interactions of [Et4N]Cl,[Pr4N]Cl and [Bu4N]Cl with protein contribute to [R4N]Cl-induced decrease thermodynamic stability of Cyt c (iii) [R4N]Cl exhibits an additive effect with denaturant to decrease thermodynamic stability and refolding rates of Cyt c (iv) low concentrations of [R4N]Cl (≤ 0.5 M) constrain the motional dynamics while the higher concentrations (>0.75 M [R4N]Cl) enhance the structural-fluctuations that denture protein (v) hydrophobicity of R-group of [R4N]Cl alters the [denaturant]-dependent conformational stability, refolding-unfolding kinetics, and CO-association kinetics of Cyt c. Furthermore, the MD simulations depicted that the addition of 1.0 M of [R4N]Cl increased the conformational fluctuations in Cyt c leading to decreased structural stability in the order [Me4N]Cl < [Et4N]Cl < [Pr4N]Cl < [Bu4N]Cl consistent with the experimental results.
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BACKGROUND: Gait abnormality detection is a challenging task in clinical practice. The majority of the current frameworks for gait abnormality detection involve the individual processes of segmentation, feature estimation, feature learning, and similarity assessment. Since each component of these modules is fixed and they are mutually independent, their performance under difficult circumstances is not ideal. We combine those processes into a single framework, a gait abnormality detection system with an end-to-end network. METHODS: It is made up of convolutional neural networks and Deep-Q-learning methods: one for coordinate estimation and the other for classification. In a single joint learning technique that may be trained together, the two networks are modeled. This method is significantly more efficient for use in real life since it drastically simplifies the conventional step-by-step approach. RESULTS: The proposed model is experimented on MATLAB R2020a. While considering into consideration the stability factor, our proposed model attained an average case accuracy of 95.3%, a sensitivity of 96.4%, and a specificity of 94.1%. SIGNIFICANCE: Our paradigm for quantifying gait analysis using commodity equipment will improve access to quantitative gait analysis in medical facilities and rehabilitation centers while also allowing academics to conduct large-scale investigations for gait-related disorders. Numerous experimental findings demonstrate the effectiveness of the proposed strategy and its ability to provide cutting-edge outcomes.
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Psoriasis, recognized as a chronic inflammatory skin disorder, disrupts immune system functionality. Global estimates by the World Psoriasis Day consortium indicate its impact on approximately 130 million people, constituting 4 to 5 percent of the worldwide population. Conventional drug delivery systems, mainly designed to alleviate psoriasis symptoms, fall short in achieving targeted action and optimal bioavailability due to inherent challenges such as the drug's brief half-life, instability, and a deficiency in ensuring both safety and efficacy. Liposomes, employed in drug delivery systems, emerge as highly promising carriers for augmenting the therapeutic efficacy of topically applied drugs. These small unilamellar vesicles demonstrate enhanced penetration capabilities, facilitating drug delivery through the stratum corneum layer of skin. This comprehensive review article illuminates diverse facets of liposomes as a promising drug delivery system to treat psoriasis. Addressing various aspects such as formulation strategies, encapsulation techniques, and targeted delivery, the review underscores the potential of liposomes in enhancing the efficacy and specificity of psoriasis treatments.
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Atreye MajumdarSambit K. MohantyObjective This article identifies and evaluates the frequency of mutations in the BCR-ABL1 kinase domain (KD) of chronic myeloid leukemia (CML) patients who showed suboptimal response to their current tyrosine kinase inhibitor (TKI) regime and assesses their clinical value in further treatment decisions. Materials and Methods Peripheral and/or bone marrow were collected from 791 CML patients. Ribonucleic acid was extracted, reverse transcribed, and Sanger sequencing method was utilized to detect single-nucleotide variants (SNVs) in BCR-ABL1 KD. Results Thirty-eight different SNVs were identified in 29.8% ( n = 236/791) patients. T315I, E255K, and M244V were among the most frequent mutations detected. In addition, one patient harbored a novel L298P mutation. A subset of patients from the abovementioned harbored compound mutations (13.3%, n = 33/236). Follow-up data was available in 28 patients that demonstrated the efficacy of TKIs in correlation with mutation analysis and BCR-ABL1 quantitation. Molecular response was attained in 50% patients following an appropriate TKI shift. A dismal survival rate of 40% was observed in T315I-harboring patients on follow-up. Conclusion This study shows the incidence and pattern of mutations in one of the largest sets of Indian CML patients. In addition, our findings strengthen the prognostic value of KD mutation analysis among strategies to overcome TKI resistance.
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The synthesis of a Schiff base-based chemosensor, denoted as H6L, was accomplished through the condensation reaction of Isophthalohydrazide and 2,6-dihydroxybenzaldehyde in an ethanol solvent. The resulting compound was further characterized using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, as well as high-resolution mass spectrometry (HRMS). Extensive research has been conducted on several facets of metal sensing phenomena, revealing that the Schiff base H6L demonstrates discerning and expeditious fluorescence sensing characteristics specifically towards Al (III) in acetonitrile. The purported method detects Al (III) can be ascribed to the suppression of photo-induced electron transfer (PET) and the enhanced chelation-induced fluorescence (CHEF). The stoichiometry of metal-ligand complexes (2:1) was determined using Job's plots titrations, HRMS and subsequently confirmed using NMR titration studies. The H6L sensors demonstrated remarkable fluorescence sensing capabilities in acetonitrile, with a low detection limit (LOD) of 0.44 µM. This LOD is suitably low for the detection of Al3+, which is commonly found in many environmental and biological systems. Fluorescence lifetime measurement provides additional evidence of complexation of H6L with Al (III). The reversibility of the sensor was demonstrated through the introduction of pyrophosphate (PPi), which forms a complex with aluminium ions, thereby releasing the chemo sensor for subsequent utilization. The findings suggest that H6L has the potential to serve as a viable probe for the detection and identification of Al3+ ions.
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Aim: The aim of this study was to compare the accuracy of two different electronic apex locators (EALs) in detecting simulated incomplete vertical root fractures (VRFs). Materials and Methods: Thirty freshly extracted single-rooted teeth were randomly divided into three groups of 10 teeth each labeled as Groups A, B, and C. Incomplete VRFs were simulated in the coronal, middle, and apical one-third of the roots for Groups A, B, and C, respectively. The teeth were embedded in alginate mold and fracture location was determined with Root ZX and Propex EALs for each sample and each group. To calculate the actual length (AL), each sample was sectioned at the upper level of the vertical fracture, and the length was measured by setting the stopper of the #10 K file under a stereomicroscope at ×30 magnification. The electronic lengths and ALs were compared using computer software, and the results were analyzed using SPSS 28.0 at a 95% confidence level. Results: No significant differences were seen in the accuracy of the two EALs when compared with ALs. Root ZX showed significantly longer measurements than ALs in groups B and C. Conclusion: The tested EALs showed low accuracy (20%) in detecting simulated incomplete VRFs with a tendency for longer measurements compared to ALs.
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Mangifera indica L. (Mango), native of tropical Asia, has enormous genetic diversity. Comparative phytochemical analysis of leaves of five varieties of Mangifera indica viz. Dashahri, Chausa, Langra, Lucknow Safeda and Gola grown in North India was carried out. Mangiferin content (using HPLC) was found to vary from 0.96 g to 3.00 g per 100 g of dry leaves. Essential oil composition (through GC-MS) showed the major components of all the five varieties to be caryophyllene (4.14-46.26%), humulene (3.19-30.45%), caryophyllene oxide (2.98-17.23%) and humulene epoxide 2 (1.56-4.73%). Results indicated that there was a direct relationship between total phenolic and flavonoid contents and DPPH radical scavenging activities. Our studies indicate that M. indica leaves, which are a form of biomass waste, could be used as an economical and renewable source of antidiabetic compound mangiferin as well as other biologically active phytoconstituents having nutraceutical as well as pharmaceutical applications.
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Nonlinear photoluminescence (N-PL) is a broadband photon emission arising from a nonequilibrium heated electron distribution generated at the surface of metallic nanostructures by ultrafast pulsed laser illumination. N-PL is sensitive to surface morphology, local electromagnetic field strength, and electronic band structure, making it relevant to probe optically excited nanoscale plasmonic systems. It also has been key to accessing the complex multiscale time dynamics ruling electron thermalization. Here, we show that plasmon-mediated N-PL emitted by a gold nanowire can be modified by an electrical architecture featuring a nanogap. Upon voltage activation, we observe that N-PL becomes dependent on the electrical transport dynamics and can thus be locally modulated. This finding brings an electrical leverage to externally control the photoluminescence generated from metal nanostructures and constitutes an asset for the development of emerging nanoscale interface devices managing photons and electrons.
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Mycobacterium tuberculosis (Mtb) type II NADH dehydrogenase (NDH-2) transports electrons into the mycobacterial respiratory pathway at the cost of reduction of NADH to NAD+ and is an attractive drug target. Herein, we have synthesised a series of 2-mercaptobenzothiazoles (C1-C14) and evaluated their anti-tubercular potential as Mtb NDH-2 inhibitors. The synthesised compounds C1-C14 were evaluated for MIC90 and ATP depletion against Mtb H37Ra, M. bovis, and Mtb H37Rv mc2 6230. Compounds C3, C4, and C11 were found to be the active molecules in the series and were further evaluated for their MIC90 against Mtb-resistant strains and for their bactericidal potential against Mtb H37Rv mc26230. The Peredox-mCherry-expressing Mtb strain was used to examine whether C3, C4, and C11 possess NDH-2 inhibitory potential. Furthermore, cytotoxicity analysis against HepG2 displayed a safety index (SI) of >10 for C3 and C4. To get an insight into the mode of interaction at NDH-2, we have performed computational analysis of our active compounds.
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Chalcones are chemical scaffolds found in natural products, particularly in plants, and are considered for structural diversity in medicinal chemistry for drug development. Herein, we designed and synthesised novel acetamide derivatives of chalcone, characterizing them using 1H NMR, 13C NMR, HRMS, and IR spectroscopic methods. These derivatives were then screened against human cancer cells for cytotoxicity using the SRB assay. Among the tested derivatives, 7g, with a pyrrolidine group, exhibited better cell growth inhibition activity against triple-negative breast cancer (TNBC) cells. Further assays, including SRB, colony formation, and fluorescent dye-based microscopic analysis, confirmed that 7g significantly inhibited MDA-MB-231 cell proliferation. Furthermore, 7g promoted apoptosis by upregulating cellular reactive oxygen species (ROS) levels and disrupting mitochondrial membrane potential (MMP). Elevated expression of pro-apoptotic proteins (Bax and caspase-3) and a higher Bax/Bcl-2 ratio with downregulation of anti-apoptotic (Bcl-2) protein levels were observed in TNBC cells. The above results suggest that 7g can promote cellular death through apoptotic mechanisms in TNBC cells.