Nutraceuticals target androgen receptor-splice variants (AR-SV) to manage castration resistant prostate cancer (CRPC).

Every year, prostate cancer is diagnosed in millions of men. The androgen receptor's (AR) unchecked activation is crucial in causing the development and progression of prostate cancer. Second-generation anti-androgen therapies, which primarily focus on targeting the Ligand Binding Domain (LBD) of AR, are effective for most patients. However, the adverse effects pose significant challenges in managing the disease. Furthermore, genetic mutations or the emergence of AR splice variants create an even more complex tumor environment, fostering resistance to these treatments. Natural compounds and their analogs, while showing a lower toxicity profile and a potential for selective AR splice variants inhibition, are constrained by their bioavailability and therapeutic efficacy. Nonetheless, recent breakthroughs in using natural derivatives to target AR and its splice variants have shown promise in treating chemoresistant castration-resistant prostate cancer (CRPC). This review will discuss the role of AR variants, particularly androgen receptor splice variant 7 (AR-V7), in CRPC and investigate the latest findings on how natural compounds and their derivatives target AR and AR splice variants.

Bridging The Gap: Essential Role of Parents and Caregivers In Their Child's Management in the Pediatric Intensive Care Unit.

The importance of parental involvement in the care and management decisions made for children hospitalized in the pediatric intensive care unit (PICU) is examined in this editorial. Initial days and weeks in a PICU can be challenging for the child and family due to the emotional intensity and medical complexity of the therapy a child receives. Regardless of the result, families may feel uncertain and anxious that their child may die or have a terrible outcome. The majority of pediatric patient deaths in hospitals happen in the PICU. Recognizing and supporting the crucial role of parents or caretakers in informed decision-making and management of their child's condition is essential for advancing prevention, detection, and treatment efforts.

Comparative Analysis of C-reactive Protein and Procalcitonin as Biomarkers for Prognostic Assessment in Pediatric Sepsis.

Background Sepsis poses a critical medical challenge due to its profound systemic inflammatory response, which frequently results in organ dysfunction and high mortality rates, especially in pediatric patients. The condition requires prompt recognition and aggressive management to mitigate its severe outcomes. Methods This prospective study enrolled 248 pediatric patients admitted with sepsis to the pediatric intensive care unit (PICU) at our tertiary care center. Patients were randomly assigned to either the C-reactive protein (CRP) or procalcitonin (PCT) groups, with biomarker levels measured upon admission (hour zero) and again at 72 hours post-admission. Clinical parameters such as the need for ionotropic support, use of steroids, incidence of acute kidney injury (AKI), requirement for invasive ventilation, patient outcomes, and changes in antibiotic management were assessed based on these biomarker levels. Results Procalcitonin-positive sepsis cases demonstrated notable clinical severity compared to their C-reactive protein counterparts, showing significantly lower systolic blood pressure (p = 0.012), heightened need for ionotropic support (p < 0.0001), and more pronounced liver and renal dysfunction as indicated by elevated serum bilirubin (p = 0.001) and creatinine levels (p = 0.0058). The incidence of AKI was also higher in procalcitonin-positive cases. Despite these severe clinical parameters, there were no significant differences in the length of the PICU stay or in patient outcomes concerning discharge and mortality rates. Procalcitonin levels effectively guided antibiotic management, resulting in therapy adjustments in a substantial proportion of cases, with 67 (54%) experiencing downgrades and 33 (27%) requiring upgrades based on procalcitonin levels measured 72 hours post-admission. Conclusion Procalcitonin proves to be a valuable biomarker in assessing the severity and management of sepsis in pediatric patients. It correlates significantly with clinical parameters such as blood pressure, the need for ionotropic support, and markers of organ dysfunction.

A Rare Presentation of Glucose-6-Phosphate Dehydrogenase Deficiency.

Approximately 400 million individuals globally experience glucose-6-phosphate dehydrogenase (G6PD) insufficiency, an enzymatic condition that may be hazardous. Because of mutations in the G6PD gene, which result in functional variants alongside a variety of biochemical and clinical symptoms, this condition is an X-linked hereditary genetic disorder. Our case is that of a 12-year-old male child who presented with acute liver failure and later on, exhibited signs of hemolysis as well. We had to rule out the possibilities of acetaminophen toxicity and hepatitis A before reaching the conclusion that an underlying G6PD deficiency was being exacerbated by viral infection and simultaneous ingestion of non-steroidal anti-inflammatory drugs (NSAIDs).

Glutaric Aciduria Presenting With an Acute Encephalitic Crisis: A Case Report.

Glutaric aciduria type 1 (GA1) is an organic aciduria inherited in an autosomal recessive pattern, with an occurrence rate of one in 100,000. It is caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase (GCDH), encoded by the GCDH gene on chromosome 19. It is an important enzyme in the catabolism of amino acids such as tryptophan, lysine, and hydroxylysine. Its deficiency leads to the accumulation of organic acids such as glutaric acid and 3-hydroxyglutaric acid, which interfere with cerebral energy metabolism and cause neurological symptoms. Here, we discuss the case of a six-month-old male child who presented with status epilepticus following an eight-day history of fever. The child was started on anti-epileptics. Initially, the child was on non-invasive ventilation and was later intubated and taken on a mechanical ventilator. A magnetic resonance imaging (MRI) scan of the brain was performed, and the findings suggested GA1. The child was started on carnitine after samples were sent for tandem mass spectrometry (TMS) and urine gas chromatography-mass spectrometry (GC/MS), which came out to be positive for GA1. Despite the timely intervention, the child did not survive. Most cases exhibit movement disorders, with many presenting in acute encephalitic crises. Additionally, a significant portion of patients experience an insidious onset of the disease. An MRI of the brain shows widened Sylvian fissures in the majority of cases. Treatment of GA1 includes dietary modifications, including a low-lysine diet and administering carnitine. Early diagnosis and management result in decreased mortality and morbidity, which underscores the need for newborn screening.

Mechanism and potentialities of photothermal and photodynamic therapy of transition metal dichalcogenides (TMDCs) against cancer.

The ultimate goal of nanoparticle-based phototherapy is to suppress tumor growth. Photothermal therapy (PTT) and photothermal photodynamic therapy (PDT) are two types of physicochemical therapy that use light radiation with multiple wavelength ranges in the near-infrared to treat cancer. When a laser is pointed at tissue, photons are taken in the intercellular and intracellular regions, converting photon energy to heat. It has attracted much interest and research in recent years. The advent of transition materials dichalcogenides (TMDCs) is a revolutionary step in PDT/PTT-based cancer therapy. The TMDCs is a multilayer 2D nano-composite. TMDCs contain three atomic layers in which two chalcogens squash in the transition metal. The chalcogen atoms are highly reactive, and the surface characteristics of TMDCs help them to target deep cancer cells. They absorb Near Infrared (NIR), which kills deep cancer cells. In this review, we have discussed the history and mechanism of PDT/PTT and the use of TMDCs and nanoparticle-based systems, which have been practiced for theranostics purposes. We have also discussed PDT/PTT combined with immunotherapy, in which the cancer cell apoptosis is done by activating the immune cells, such as CD8+.

Exposure of environmental trace elements in prostate cancer patients: A multiple metal analysis.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. To elucidate the connection between trace elements (arsenic: As, cadmium: Cd, lead: Pb, chromium: Cr, and nickel: Ni) and the risk of PCa, we analyzed trace element levels in the serum, urine, and tissues of PCa patients, while also examining their smoking status. We correlated these levels with their smoking habits. Notably, levels of Cd (P ≤ 0.05) and As (P ≤ 0.01) were significantly higher in the tumor tissue than in adjacent tissues. No significant differences were observed in the levels of Pb, Cr and Ni. Additionally, urinary Cd levels in 70% and arsenic levels in 2.3% of the PCa cohort were markedly higher than the CDC-reported cutoff (Cd ≤ 0.185 µg/L & As ≤100 µg/L). None displayed elevated levels of urinary Pb, Cr, and Ni. Conversely, in serum samples, the concentration of arsenic exceeded the CDC-determined limit (As ≤1.0 µg/L) in 31.69% of PCa patients. However, only 7.04% of patients had higher serum Cd levels than the CDC standard values (Cd ≤ 0.315 µg/L), while all PCa patients exceeded the Cr CDC limit (Cr ≤ 0.16 µg/L) and the Ni CDC limit (Ni ≤ 0.2 µg/L). On the contrary, no significant differences were observed in serum Pb (Pb ≤ 35.0 µg/L). Our findings establish a positive link between Cd and arsenic tissue concentrations and the risk of PCa. Subsequent studies are essential to determine whether elevated trace element levels pose a risk for the development of prostate carcinogenesis. Interestingly, among the PCa cohort comprising smokers, notably higher Cd levels were observed only in tumor tissues (P ≤ 0.01) and urine (P ≤ 0.05) compared to other elements or in other specimens.

Hypothesizing the Green Synthesis of Tamoxifen Loaded Magnetic Nanoparticles for the Treatment of Breast Cancer.

RESEARCH BACKGROUND: Breast cancer is the second leading cause of death all over the world and is not only limited to females but also affects males. For estrogen receptor-positive breast cancer, tamoxifen has been considered the gold-line therapy for many decades. However, due to the side effects associated with the use of tamoxifen, its use is only limited to individuals in high-risk groups and limits its clinical application to moderate and/or lower-risk groups. Thus, there is a necessity to decrease the dose of tamoxifen, which can be achieved by targeting the drug to breast cancer cells and limiting its absorption to other body parts. PROBLEM STATEMENT: Artificial antioxidants used in the formulation preparation are assumed to upsurge the risk of cancer and liver damage in humans. The need of the hour is to explore bio-efficient antioxidants from natural plant sources as they are safer and additionally possess antiviral, anti-inflammatory, and anticancer properties. Objectives of the study and research: The objective of this hypothesis is to prepare tamoxifen-loaded PEGylated NiO nanoparticles using green chemistry, tumbling the toxic effects of the conventional method of synthesis for targeted delivery to breast cancer cells. Significance of the research work: The significance of the work is to hypothesize a green method for the synthesis of NiO nanoparticles that are eco-friendly, cost-effective, decrease multidrug resistance, and can be used for targeted therapy. Garlic extract contains an organosulfur compound (Allicin) which has drug-metabolizing, anti-oxidant, and tumour growth inhibition effects. In breast cancer, allicin sensitizes estrogen receptors, increasing the anticancer efficacy of tamoxifen and reducing offsite toxicity. Thus, this garlic extract would act as a reducing agent and a capping agent. The use of nickel salt can help in targeted delivery to breast cancer cells and, in turn, reduces drug toxicity in different organs. Future directions/recommendations: This novel strategy may aim for cancer management with less toxic agents acting as an apt therapeutic modality.

Occurrence of Dirofilaria immitis infection in shelter cats in the lower Rio Grande Valley region in South Texas, United States, using integrated diagnostic approaches.

Dirofilaria immitis is a mosquito-borne filarioid nematode that affects dogs and cats. Although heartworm infections in cats can be fatal, it is commonly neglected by cat owners and veterinarians. Moreover, diagnosing heartworm infection in cats can be challenging, requiring the integration of multiple laboratorial tests and clinical examination. The objective of this study was to estimate the occurrence of D. immitis infection in shelter cats in the Lower Rio Grande Valley (RGV) region of Texas using a combination of immunodiagnostic and molecular methods. The RGV has a large population of stray animals with limited access to veterinary care. One hundred and twenty-two paired samples of serum and DNA extracted from the blood clots of cats from 14 towns in this region were analyzed. Serum samples were used for heartworm antibody detection (Heska® Solo Step®), and heartworm antigen detection using a commercial ELISA kit (DiroCHEK®) pre- and post-immune-complex dissociation (ICD) via heat treatment. A species-specific probe-based qPCR assay targeting a fragment of the cytochrome oxidase c subunit 1 of the mitochondrial DNA was utilized to detect the presence of parasite DNA. Twenty-two cats (18%) were positive in at least one diagnostic test. Antibody testing detected most cases (19/122; 15.6%); pre- and post-ICD antigen testing detected 6 cases (6/122; 4.9%); and qPCR detected the fewest cases (4/122; 3.3%), with 2 cats positive on all three diagnostic tests. Veterinarians should encourage local cat owners to utilize year-round heartworm prevention.

Heavy metals contamination in sediments of Bharalu river, Guwahati, Assam, India: A tributary of river Brahmaputra.

This study aimed to assess heavy metals in the surface sediments of the Bharalu river, India. Metal concentrations ranged from 6.65-54.6 mg/kg for Ni, 25.2-250.0 mg/kg for Zn, 83.3-139.1 mg/kg for Pb, and 11940.0-31250.0 mg/kg for Fe. The level of metal contamination was assessed using sediment quality guidelines, geo-accumulation index (Igeo), enrichment factor (EF), pollution Load Index (PLI),Nemerow's pollution index (PIN), and potential ecological risk index. Pb exceeded the sediment quality guidelines at all sites indicating a potential threat to the river ecosystem. (Igeo) and EF also showed moderate to severe enrichment for Pb. Potential ecological risk (RI) showed low risk in the sediments, and Pb is the major contributor to ecological risk. Overall, pollution indices revealed comparably higher contamination of the sediments in the downstream sites than in the upstream site. PCA and correlation matrix analysis indicated both anthropogenic and natural origins for metals. Among anthropogenic sources, urban discharges and waste dumping could be mainly attributed to metal contamination in the river sediments. These findings may aid in developing future river management methods explicitly aimed at tackling heavy metal pollution to prevent further damage to the river ecosystem.

Superparamagnetic Iron-Oxide Nanoparticles Synthesized via Green Chemistry for the Potential Treatment of Breast Cancer.

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of -30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 µM and 6.29 ± 0.21 µM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications.

Folic acid engineered sulforaphane loaded microbeads for targeting breast cancer.

Non-targeted cancer therapy poses a huge risk to the cancer patients' life due to high toxicity offered by chemotherapy. Breast carcinoma is one of such deleterious disease, demanding a highly effectual treatment option which could reduce the toxicity and extend survival rate. Since, folate receptors extensively display themselves on the cancer cell surface, targeting them would help to ameliorate the progression and metastasis. Considering this, we envisaged and developed sulforaphane loaded folate engineered microbeads to target breast cancer cells over-expressing folate receptors. The surface engineered microbeads were optimized and developed using emulsion gelation technique, among which the best developed preparation demonstrated the particle size of 1302 ± 3.98 µm, % EE of 84.1 ± 3.32% and in vitro drug release of 98.1 ± 4.42%@24h. The spherical sized microbead showed controlled release with improved haem-compatibility in comparison to the bare drug. Free radical scavenging activity by ABTS assay showed strong anti-oxidant activity (IC50 20.62 µg/ml) of the targeted microbeads with profound cancer cell sup pressing effect (IC50 17.48 ± 3.5 µM) as observed in MCF-7 cells by MTT assay. Finally, in comparison to lone SFN, the targeted therapy showed enhanced uptake by the intestinal villi indicating a suitable oral targeted therapy against breast carcinoma.

Deciphering the role of gut metabolites in non-alcoholic fatty liver disease.

Perturbations in microbial abundance or diversity in the intestinal lumen leads to intestinal inflammation and disruption of intestinal membrane which eventually facilitates the translocation of microbial metabolites or whole microbes to the liver and other organs through portal vein. This process of translocation finally leads to multitude of health disorders. In this review, we are going to focus on the mechanisms by which gut metabolites like SCFAs, tryptophan (Trp) metabolites, bile acids (BAs), ethanol, and choline can either cause the development/progression of non-alcoholic fatty liver disease (NAFLD) or serves as a therapeutic treatment for the disease. Alterations in some metabolites like SCFAs, Trp metabolites, etc., can serve as biomarker molecules whereas presence of specific metabolites like ethanol definitely leads to disease progression. Thus, proper understanding of these mechanisms will subsequently help in designing of microbiome-based therapeutic approaches. Furthermore, we have also focussed on the role of dysbiosis on the mucosal immune system. In addition, we would also compile up the microbiome-based clinical trials which are currently undergoing for the treatment of NAFLD and non-alcoholic steatohepatitis (NASH). It has been observed that the use of microbiome-based approaches like prebiotics, probiotics, symbiotics, etc., can act as a beneficial treatment option but more research needs to be done to know how to manipulate the composition of gut microbes.

Erratum: A model system for antiviral siRNA therapeutics using exosome-based delivery.

[This corrects the article DOI: 10.1016/j.omtn.2022.08.011.].

A model system for antiviral siRNA therapeutics using exosome-based delivery.

Emerging viral diseases, such as Ebola, SARS, MERS, and the pathogen causing COVID-19, SARS-CoV-2, present a challenge for the development of therapeutics because of strict biosafety handling procedures and rapid mutation of their genomes. To facilitate the development of an adaptable and testable therapeutic model system, a colostrum exosome-based nanoparticle delivery system, EPM (exosome-PEI matrix), that overcomes stringent biosafety containment, was used to mimic the expression of viral proteins. This system would greatly expand the number of laboratories actively participating in the screening of potential therapeutics. EPM technology can deliver both plasmid DNA and siRNA to both simulate viral gene expression and screen potential antiviral siRNA therapeutics. Using this nanoplatform, three key SARS-CoV-2 proteins (the spike glycoprotein, nucleocapsid, and replicase) were expressed in vitro and in vivo. In vitro, several viral gene-targeting siRNAs were screened to determine knockdown efficiency, with some siRNA duplexes resulting in 80%-95% knockdown of corresponding protein expression. Moreover, in vivo experiments introducing the spike protein and nucleocapsid by EPM resulted in the production of antibodies against the viral antigen, measured up to 45 d after target delivery. Together, these findings support the efficacy of the EPM delivery system to establish a model for screening antiviral therapeutics-reduced biosafety level.

PSO-Based Evolutionary Approach to Optimize Head and Neck Biomedical Image to Detect Mesothelioma Cancer.

Mesothelioma is a form of cancer that is aggressive and fatal. It is a thin layer of tissue that covers the majority of the patient's internal organs. The treatments are available; however, a cure is not attainable for the majority of patients. So, a lot of research is being done on detection of mesothelioma cancer using various different approaches; but this paper focuses on optimization techniques for optimizing the biomedical images to detect the cancer. With the restricted number of samples in the medical field, a Relief-PSO head and mesothelioma neck cancer pathological image feature selection approach is proposed. The approach reduces multilevel dimensionality. To begin, the relief technique picks different feature weights depending on the relationship between features and categories. Second, the hybrid binary particle swarm optimization (HBPSO) is suggested to automatically determine the optimum feature subset for candidate feature subsets. The technique outperforms seven other feature selection algorithms in terms of morphological feature screening, dimensionality reduction, and classification performance.

Identification and Classification of Prostate Cancer Identification and Classification Based on Improved Convolution Neural Network.

Prostate cancer is one of the most common cancers in men worldwide, second only to lung cancer. The most common method used in diagnosing prostate cancer is the microscopic observation of stained biopsies by a pathologist and the Gleason score of the tissue microarray images. However, scoring prostate cancer tissue microarrays by pathologists using Gleason mode under many tissue microarray images is time-consuming, susceptible to subjective factors between different observers, and has low reproducibility. We have used the two most common technologies, deep learning, and computer vision, in this research, as the development of deep learning and computer vision has made pathology computer-aided diagnosis systems more objective and repeatable. Furthermore, the U-Net network, which is used in our study, is the most extensively used network in medical image segmentation. Unlike the classifiers used in previous studies, a region segmentation model based on an improved U-Net network is proposed in our research, which fuses deep and shallow layers through densely connected blocks. At the same time, the features of each scale are supervised. As an outcome of the research, the network parameters can be reduced, the computational efficiency can be improved, and the method's effectiveness is verified on a fully annotated dataset.

Enhancing the performance of BN nanosheets as promising anode material for Li-ion batteries with carbon-doping.

Li-ion batteries (LIB) are an integral part of portable electronic gadgets. Enhancing the performance of LIB is an active area of research. Here, we investigated the lithiation properties of pure and C-doped BN (BCN) nanosheets using density functional theory. Our calculations show that adsorption energy (Ead) significantly improves via C-doping and it is reciprocal to Li concentration. Depending on Ead, BCN exhibits a wider range of theoretical specific capacity and open circuit voltage (OCV). We obtained a remarkable specific capacity of 778.50 mAhg-1 with an OCV of 0.72 V. A significant charge transfer (0.3e) is also witnessed from Li to nanosheet at local level. A semiconductor to metallic transition is also predicted for higher Li coverage, which pledges for enhanced rate capability. Molecular dynamic analysis indicates that BCN recovers the structural deformations during charging and discharging process. Present calculations show that BCN could be a promising anode material in LIB.

Using QMRA to understand possible exposure risks of SARS-CoV-2 from the water environment.

This study investigated the human risk of infection due to inadvertent ingestion of water during swimming in a river that receives SARS-CoV-2-containing effluent from a wastewater treatment plant (WWTP). A quantitative microbial risk assessment (QMRA) approach was applied for risk estimation using dose-response models (DRM) of different surrogate coronaviruses (SARS-CoV-1, MERS-CoV) and the virus responsible for most infectious respiratory illnesses (i.e., influenza A H5N1) due to the unavailability of DRM for SARS-CoV-2. The ratio of infectious concentration to genomic copies of SARS-CoV-2 is unknown and also unavailable for other coronaviruses. Therefore, literature-based information on enteric viruses was used for formulating the ratio used for QMRA, although it is acknowledged that identifying this information for SARS-CoV-2 is a priority, and in the absence of information specific to SARS-CoV-2, another coronavirus would be a preferable surrogate to the enteric viruses used here. The calculated concentration of ingested SARS-CoV-2 ranged between 4.6 × 10-7 and 80.5 genomic copies/dip (one swim = 32 mL). The risk of infection (> 9 × 10-12 to 5.8 × 10-1) was found to be > 1/10,000 annual risk of infection. Moreover, the study revealed that the risk estimation was largely dependent on the value of the molecular concentration of SARS-CoV-2 (gc/mL). Overall immediate attention is required for obtaining information on the (i) ratio of infectious virus to genomic copies, (ii) DRM for SARS-CoV-2, and (iii) virus reduction rate after treatment in the WWTPs. The QMRA structure used in present findings is helpful in analyzing and prioritizing upcoming health risks due to swimming performed in contaminated rivers during the COVID-19 outbreak.

Anthocyanidins Inhibit Growth and Chemosensitize Triple-Negative Breast Cancer via the NF-κB Signaling Pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is the only systemic treatment option. Although chemotherapeutic drugs respond initially in TNBC, many patients relapse and have a poor prognosis. Poor survival after metastatic relapse is largely attributed to the development of resistance to chemotherapeutic drugs. In this study, we show that bilberry-derived anthocyanidins (Anthos) can inhibit the growth and metastasis of TNBC and chemosensitize paclitaxel (PAC)-resistant TNBC cells by modulating the NF-κB signaling pathway, as well as metastatic and angiogenic mediators. Anthos administered orally significantly decreased MDA-MB-231 orthoxenograft tumor volume and led to lower rates of lymph node and lung metastasis, compared to control. Treatment of PAC-resistant MDA-MB-231Tx cells with Anthos and PAC in combination lowered the IC50 of PAC by nearly 20-fold. The combination treatment also significantly (p < 0.01) decreased the tumor volume in MDA-MB-231Tx orthoxenografts, compared to control. In contrast, Anthos and PAC alone were ineffective against MDA-MB-231Tx tumors. Our approach of using Anthos to inhibit the growth and metastasis of breast cancers, as well as to chemosensitize PAC-resistant TNBC, provides a highly promising and effective strategy for the management of TNBC.