Chemical analysis and biological activities on solvent extracts from different parts of Rhus chinensis mill.

The present research is focused on the preparation of a variety of solvent extracts using different parts of Rhus chinensis Mill. for the estimation of phytochemicals and to perform biological activities. The highest phenolic and flavonoid contents were recorded as 141.48 ± 0.67 mg GAE/g in methanol root extract and 54.34 ± 0.28 mg QE/g in ethyl acetate root extract. Ethyl acetate root extract displayed an IC50 of 7.83 ± 0.18 µg/mL in the DPPH assay. TPC and TFC were found moderately correlated with antioxidant activity. The root and leaf extracts showed antibacterial activities comparable to those of standard drugs against the gram-positive and gram-negative bacteria. The MIC and MBC for root extract against Staphylococcus aureus were 7.8125 mg/mL and 15.625 mg/mL respectively. Similarly, the MIC and MBC for leaf extract against Escherichia coli were 15.625 mg/mL and 31.25 mg/mL respectively.

Advancing Measurement-Informed Care in Outpatient Community Behavioral Health.

Measurement-informed care (MIC), also known as measurement-based care or patient-reported outcomes, for behavioral health conditions has had low uptake in the United States. To advance MIC in the near term, the authors reviewed nationally endorsed behavioral health measures and worked with national experts to recommend a core set of outpatient measures to prioritize for use. The resulting set of measures is for common behavioral and comorbid conditions and is outcomes based, low burden, and suitable for value-based payment. The panel of national experts also recommended developing a consensus on quality-of-life measures and functional measures for use across diagnostic categories of the core set.

Visual detection of fungicide resistance by combining RPA and CRISPR/Cas12a in peach Brown rot fungus Monilinia fructicola.

BACKGROUND: Peach brown rot caused by Monilinia fructicola severely affects the quality and yield of peach, resulting in large economic losses worldwide. Methyl benzimidazole carbamate (MBC) fungicides and sterol demethylation inhibitor (DMI) fungicides are among the most applied chemical classes used to control the disease but resistance in the target pathogen has made them risky choices. Timely monitoring of resistance to these fungicides in orchards could prevent control failure in practice. RESULTS: In the current study, we developed methods based on recombinase polymerase amplification (RPA) and CRISPR/Cas12a systems to detect MBC and DMI resistance based on the E198A mutation in the ß-tubulin (MfTub2) gene and the presence of the Mona element in the upstream region of the MfCYP51, respectively. For MBC resistance, RPA primers were designed that artificially incorporated PAM sites to facilitate the CRISPR/Cas12a reaction. Subsequently, specific tcrRNAs were designed based on the E198A mutation site. For the detection of the Mona element, we designed RPA primers M-DMI-F2/M-DMI-R1 that in combination with crRNA1 detected 'Mona' and distinguished resistant from sensitive strains. CONCLUSION: Both methods exhibited high sensitivity and specificity, requiring only a simple isothermal device to obtain results within 1 h at 37 °C. The FQ-reporter enabled visualization with a handheld UV or white light flashlight. This method was successfully used with purified DNA from lab cultures and crude DNA from symptomatic fruit tissue, highlighting its potential for on-site detection of resistant strains in orchards. © 2024 Society of Chemical Industry.

Dupilumab treatment decreases MBC2s, correlating with reduced IgE levels in pediatric atopic dermatitis.

BACKGROUND: A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, an mAb targeting the IL-4 receptor α (IL-4Rα) subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B cells, critical in atopic diseases. Recent studies indicate IgG+CD23hiIL-4Rα+ type 2 memory B cells (MBC2s) as IgE-producing B-cell precursors, linked to total IgE serum levels in atopic patients. Total IgE serum levels decreased during dupilumab treatment in previous studies. OBJECTIVE: We sought to assess the effects of dupilumab treatment in comparison with alternative therapies on the frequency of MBC2s and the correlation to total IgE levels in pediatric patients with AD. METHODS: Pediatric patients with AD, participating in an ongoing trial, underwent randomization into 3 treatment groups: dupilumab (n = 12), cyclosporine (n = 12), and topical treatment (n = 12). Plasma samples and PBMCs were collected at baseline (T0) and at 6 months after starting therapy (T6). Flow cytometry was used for PBMC phenotyping, and ELISA was used to assess total IgE levels in plasma. RESULTS: Our findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. In addition, a significant correlation was observed between MBC2s and total IgE levels. CONCLUSIONS: Systemic blocking of the IL-4Rα subunit leads to a decrease in circulating MBC2 cells and total IgE levels in pediatric patients with AD. Our findings unveiled a novel mechanism through which dupilumab exerts its influence on the atopic signature.

Determination of bactericidal activity against 3HC-2-Tre-labelled Mycobacterium abscessus (Mycobacteroides abscessus) by automated fluorescence microscopy.

The minimum bactericidal concentration (MBC) of antibiotics is an important parameter for the potency of a drug in eradicating a bacterium as well as an important measure of the potential of a drug candidate in research and development. We have established a fluorescence-based microscopy method for the determination of MBCs against the non-tuberculous mycobacterium Mycobacterium abscessus (Mycobacteroides abscessus) to simplify and accelerate the performance of MBC determination compared to counting colony forming units on agar. Bacteria are labelled with the trehalose-coupled dye 3HC-2-Tre and analysed in a 96-well plate. The results of the new method are consistent with MBC determination by plating on agar. The method was used to evaluate the bactericidality of the antibiotics rifabutin, moxifloxacin, amikacin, clarithromycin and bedaquiline. Bactericidal effects against M. abscessus were observed, which are consistent with literature data.

Male Breast Cancer: Current Scenario and Future Perspectives.

Male breast cancer (MBC), one of the rare types of cancer among men where the global incidence rate is 1.8% of all breast cancers cases with a yearly increase in a pace of 1.1%. Since the last 10 years, the incidence has been increased from 7.2% to 10.3% and the mortality rate was decreased from 11% to 3.8%. Nevertheless, the rate of diagnoses has been expected to be around 2.6% in the near future, still there is a great lack in studies to characterize the MBC including the developed countries. Based on our search, it is evidenced from the literature that the number of risk factors for the cause of MBC are significant, which includes the increase in age, family genetic history, mutations in specific genes due to various environmental impacts, hormonal imbalance and unregulated expression receptors for specific hormones of high levels of estrogen or androgen receptors compared to females. MBCs are broadly classified into ductal and lobular carcinomas with further sub-types, with some of the symptoms including a lump or swelling in the breast, redness of flaky skin in the breast, irritation and nipple discharge that is similar to the female breast cancer (FBC). The most common diagnostic tools currently in use are the ultrasound guided sonography, mammography, and biopsies. Treatment modalities for MBC include surgery, radiotherapy, chemotherapy, hormonal therapy, and targeted therapies. However, the guidelines followed for the diagnosis and treatment modalities of MBC are mostly based on FBC that is due to the lack of prospective studies related to MBC. However, there are distinct clinical and molecular features of MBC, it is a need to develop different clinical methods with more multinational approaches to help oncologist to improve care for MBC patients.

The burden of antibiotic resistance of the main microorganisms causing infections in humans - review of the literature.

One of the biggest threats to human well-being and public health is antibiotic resistance. If allowed to spread unchecked, it might become a major health risk and trigger another pandemic. This proves the need to develop antibiotic resistance-related global health solutions that take into consideration microdata from various global locations. Establishing positive social norms, guiding individual and group behavioral habits that support global human health, and ultimately raising public awareness of the need for such action could all have a positive impact. Antibiotic resistance is not just a growing clinical concern but also complicates therapy, making adherence to current guidelines for managing antibiotic resistance extremely difficult. Numerous genetic components have been connected to the development of resistance; some of these components have intricate paths of transfer between microorganisms. Beyond this, the subject of antibiotic resistance is becoming increasingly significant in medical microbiology as new mechanisms underpinning its development are identified. In addition to genetic factors, behaviors such as misdiagnosis, exposure to broad-spectrum antibiotics, and delayed diagnosis contribute to the development of resistance. However, advancements in bioinformatics and DNA sequencing technology have completely transformed the diagnostic sector, enabling real-time identification of the components and causes of antibiotic resistance. This information is crucial for developing effective control and prevention strategies to counter the threat.

A BERT-GNN Approach for Metastatic Breast Cancer Prediction Using Histopathology Reports.

Metastatic breast cancer (MBC) continues to be a leading cause of cancer-related deaths among women. This work introduces an innovative non-invasive breast cancer classification model designed to improve the identification of cancer metastases. While this study marks the initial exploration into predicting MBC, additional investigations are essential to validate the occurrence of MBC. Our approach combines the strengths of large language models (LLMs), specifically the bidirectional encoder representations from transformers (BERT) model, with the powerful capabilities of graph neural networks (GNNs) to predict MBC patients based on their histopathology reports. This paper introduces a BERT-GNN approach for metastatic breast cancer prediction (BG-MBC) that integrates graph information derived from the BERT model. In this model, nodes are constructed from patient medical records, while BERT embeddings are employed to vectorise representations of the words in histopathology reports, thereby capturing semantic information crucial for classification by employing three distinct approaches (namely univariate selection, extra trees classifier for feature importance, and Shapley values to identify the features that have the most significant impact). Identifying the most crucial 30 features out of 676 generated as embeddings during model training, our model further enhances its predictive capabilities. The BG-MBC model achieves outstanding accuracy, with a detection rate of 0.98 and an area under curve (AUC) of 0.98, in identifying MBC patients. This remarkable performance is credited to the model's utilisation of attention scores generated by the LLM from histopathology reports, effectively capturing pertinent features for classification.

Estimation of MBC: MIC Ratio of Herbal Extracts against Common Endodontic Pathogens.

Herbal extracts have evoked interest owing to the small number of terpenoids and phenolic compounds, which impart antimicrobial, antioxidant, and anti-inflammatory properties. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of four herbal extracts (lemon grass oil, basil oil, peppermint oil, and Obicure tea extract) against endodontic pathogens along with the MIC: MBC/MFC ratio were evaluated. The antimicrobial activity by detecting the MIC of three essential oils and tea extract was evaluated against eight common endodontic pathogens by the broth dilution method, while MBC was detected by subculturing onto blood agar from the first -three to five tubes from the MIC dilution tubes (showing no turbidity), which were plated on blood agar. All herbal extracts proved to be effective antimicrobials against tested endodontic pathogens. Basil oil had a bacteriostatic effect on all the organisms (P < 0.05). Mint oil showed bacteriostatic activity on Enterococcus (E.) faecalis and Peptostreptococcus (P > 0.05). Tea extract had a bacteriostatic effect (P > 0.05) against all tested microbes except Actinomyces, Lactobacilli, Staphylococcus (S.) aureus, and Fusobacterium (F.) nucleatum. Lemon grass oil had a bactericidal effect against all the organisms and a bacteriostatic effect against Peptostreptococcus (P > 0.05). It can be concluded that basil oil showed a strong bactericidal effect on the test organisms. The MIC for the organisms ranged from 0.2 to 50 µg/ml.

Mechanistic Study of Antimicrobial Effectiveness of Cyclic Amphipathic Peptide [R4W4] against Methicillin-Resistant Staphylococcus aureus Clinical Isolates.

Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP.

Psychosocial and supportive care concerns of young women living with advanced breast cancer: baseline findings from a prospective virtual support intervention study.

PURPOSE: Adolescent and young adults (AYAs) with metastatic breast cancer (MBC) experience high physical and psychosocial burdens compounded by a disrupted life trajectory. We sought to determine the psychosocial and supportive care concerns of this population to better understand and address unmet needs. METHODS: AYAs diagnosed with MBC (18-39 years) participating in a prospective interventional study (Young, Empowered, and Strong) at Dana-Farber Cancer Institute completed an electronic survey following enrollment. Measures evaluated sociodemographics, health behaviors, quality of life, and symptoms, among others. We used two-sided Fisher's exact tests to determine associations between concerns (e.g., cancer progression, side effects, lifestyle, finances, fertility) and demographic variables. RESULTS: Among 77 participants enrolled from 9/2020-12/2022, average age at MBC diagnosis and survey was 35.9 (range: 22-39) and 38.3 years (range: 27-46), respectively. Most were non-Hispanic white (83.8%) and 40.3% reported their diagnosis caused some financial problems. Many were concerned about fertility (27.0%), long-term treatment side effects (67.6%), exercise (61.6%), and diet (54.1%). Select concerns varied significantly by age, race/ethnicity, and education. Younger women at survey reported greater concern about familial cancer risk (p = 0.028). Women from minority racial/ethnic groups more frequently reported issues talking about their cancer to family/friends (p = 0.040) while those with more education were more frequently concerned with long-term effects of cancer on their health (p = 0.021). CONCLUSION: Young women living with MBC frequently report psychosocial, health, and cancer management concerns. Tailoring supportive care and communications to address prevalent concerns including disease progression and treatment side effects may optimize wellbeing.

Green Synthesized Chitosan Nanoparticles for Controlling Multidrug-Resistant mecA- and blaZ-Positive Staphylococcus aureus and aadA1-Positive Escherichia coli.

Antimicrobial resistance has recently been considered an emerging catastrophe globally. The public health and environmental threats were aggravated by the injudicious use of antibiotics in animal farming, aquaculture, and croup fields, etc. Consequently, failure of antibiotic therapies is common because of the emergence of multidrug-resistant (MDR) bacteria in the environment. Thus, the reduction in antibiotic spillage in the environment could be an important step for overcoming this situation. Bear in mind, this research was focused on the green synthesis of chitosan nanoparticles (ChiNPs) using Citrus lemon (Assam lemon) extract as a cross-linker and application in controlling MDR bacteria to reduce the antibiotic spillage in that sector. For evaluating antibacterial activity, Staphylococcus aureus and Escherichia coli were isolated from environmental specimens, and their multidrug-resistant pattern were identified both phenotypically by disk diffusion and genotypically by detecting methicillin- (mecA), penicillin- (blaZ), and streptomycin (aadA1)-resistance encoding genes. The inhibitory zone's diameter was employed as a parameter for determining the antibacterial effect against MDR bacteria revealing 30 ± 0.4 mm, 34 ± 0.2 mm, and 36 ± 0.8 mm zones of inhibition against methicillin- (mecA) and penicillin (blaZ)-resistant S. aureus, and streptomycin (aadA1)-resistant E. coli, respectively. The minimum inhibitory concentration at 0.31 mg/mL and minimum bactericidal concentration at 0.62 mg/mL of yielded ChiNPs were used as the broad-spectrum application against MDR bacteria. Finally, the biocompatibility of ChiNPs was confirmed by showing a negligible decrease in BHK-21 cell viability at doses less than 2 MIC, suggesting their potential for future application in antibiotic-free farming practices.

The Effects of Encapsulation on the In Vitro Anti-Clostridial Activity of Olive Mill Wastewater Polyphenolic Extracts: A Promising Strategy to Limit Microbial Growth in Food Systems.

Despite the technologies applied to food production, microbial contamination and chemical deterioration are still matters of great concern. In order to limit these phenomena, new natural approaches should be applied. In this context, the present study aimed to assess the antioxidant and anti-Clostridial effects of two different polyphenolic extracts derived from olive mill vegetation water, one liquid (LE) and one encapsulated (EE). The extracts have been preliminary characterized using Liquid Chromatography Quadrupole Time-Of Flight spectrometry. The Oxygen Radical Absorbance Capacity method was used to determine the antioxidant capacity, registering a higher value for EE compared to that for LE (3256 ± 85 and 2446 ± 13 µgTE/g, respectively). The antibacterial activity against C. perfringens, C. botulinum and C. difficile was studied by the agar well diffusion method, MIC and MBC determination and a time-kill test. The results confirm that EE and LE are able to limit microbial growth, albeit with minor effects when the phenolic compounds are encapsulated. Further studies are needed to evaluate the possible application of these extracts in food systems.

Determination of total phenolics, flavonoids, and testing of antioxidant and antibacterial activities of red ginger (Zingiber officinale var. Rubrum).

Objective: The purpose of this study was to select the active fraction of red ginger (Zingiber officinale var. Rubrum) for its antioxidant and antibacterial activities against Staphylococcus aureus (AMC 6934), Bacillus subtilis (AMC 7923), Pseudomonas aeruginosa (AMC 8973), and Escherichia coli (AMC 5761). Materials and Methods: A total of 2 kg of dry red ginger rhizome powder was macerated in stages with different levels of solvent polarity to extract the chemical composition within the red ginger powder sample. The extraction process begins with a non-polar solvent (n-hexane) by soaking the red ginger powder sample for 3 × 24 h. Results: The red ginger extract fractionated with methanol produced alkaloids, phenolics, flavonoids, and coumarins, while the fractionation using n-hexane produced alkaloids and triterpenoids only. The fractionation with ethyl acetate produced alkaloids, phenolics, flavonoids, triterpenoids, saponins, and coumarins. The antioxidant activity test was 49.261 mg/l for the ethyl acetate fraction, 146.648 mg/l for the methanol fraction, and 300.865 mg/l for the n-hexane fraction. Conclusion: The ethyl acetate fraction was effectively powerful in inhibiting the growth of Gram-positive and Gram-negative bacteria. All fractions had moderate antibacterial activity; however, the performance of ethyl acetate in the red ginger extract was better than that of methanol and n-hexane.

A Unique Surgical Case of Mixed Metaplastic Breast Carcinoma With Heterologous Mesenchymal Differentiation and Conventional Adenocarcinomatous Elements.

Metaplastic breast carcinoma (MBC) is very rare among all invasive breast carcinomas, accounting for less than 1.0% of them. MBCs are classified into five subtypes, including mixed MBC - where the mix might be multiple metaplastic elements or a mixture of epithelial and mesenchymal elements. Overall survival for mixed MBC tends to correlate with a significantly worse outcome. Therefore, an early accurate diagnosis and surgical treatment for mixed MBCs must allow for an improved quality of life and better prognosis. However, there have not been many recently published papers describing the detailed cytological features of mixed MBCs on fine-needle aspiration (FNA) specimens. A 60-year-old female presented with a history of a hard breast mass on the left lateral side, showing an ill-defined and marginally enhanced tumor nodule on magnetic resonance imaging. The cytologic specimens of FNA contained a large number of three-dimensional, cohesive and sheet-like clusters, or non-cohesive single cells, of highly atypical spindled sarcomatoid to oval epithelioid cells having hyperchromatic pleomorphic nuclei and mitotic figures, in a necrotic and hemorrhagic background. A small amount of osteoid matrix-like substance was rarely seen, associated with a very small number of osteoclast-like giant cells. We first interpreted it as an invasive breast carcinoma of high grade. A mastectomy was performed, and a gross examination of the neoplasm revealed a hemorrhagic solid tumor lesion with a gray-whitish cut surface, measuring approximately 35 × 24 × 21 mm in diameter. On a microscopic examination, the tumor was predominantly composed of the proliferation of highly atypical oval to spindled cells predominantly in a sarcomatous growth fashion with focal production of chondroid and osteoid matrix, peripherally coexisted with a smaller volume of conventional invasive breast carcinoma. Immunohistochemistry showed that the sarcomatous tumor cells were specifically positive for vimentin, α-smooth muscle actin, or epithelial membrane antigen. Therefore, we finally made a diagnosis of invasive mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements. To the best of our knowledge, this would most recently be the first case report of mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements, with a focus on its FNA cytomorphologic findings. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of MBC, based on multiple and adequate samplings.

Pleomorphic/solid lobular carcinoma of male breast with PALB2 germline mutation: case report and literature review.

Male breast cancer (MBC) accounts for approximately 1% of all breast cancers and among these infiltrating lobular carcinomas (ILC) represents only 1-2% of all MBC cases. Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of ILC with only eight cases reported until now in males. Up to 10% of MBC cases have a germline pathogenic variant in a predisposing gene such as BRCA1 and BRCA2 genes. Mutations in PALB2 (partner and localizer of BRCA2) have been reported in men with breast cancer, with a frequency that ranges from 0.8 to 6.4%, but it has never been reported in male ILC. Here, we report a rare and interesting case of an invasive pleomorphic/solid lobular carcinoma, which carries a pathogenic variant in PALB2 gene, and a family history of breast cancer without other well defined risk factors for developing this type of neoplasia. In addition, we review the current literature.

The prognostic value of absolute lymphocyte count and neutrophil-to-lymphocyte ratio for patients with metastatic breast cancer: a systematic review and meta-analysis.

Background: Neutrophil-to-lymphocyte ratio (NLR) is considered a potential prognostic marker in early breast cancer. However, the prognosis of absolute lymphocyte count (ALC) and NLR in metastatic breast cancer (MBC) has been reported in a few studies, and conclusions are still conflicting. This present manuscript aims to provide further solid evidence regarding the prognostic values of ALC and NLR in MBC patients. Method: Eligible studies that reported the associations between ALC or NLR and MBC were included by searching relative electronic databases. Overall survival (OS) and progression-free survival (PFS) were used as outcome measures. The hazard ratio (HR) values and 95% confidence interval (CI) of the outcome measures were collected as effect sizes, and further analysis and discussion were conducted according to the pooled HR, subgroup analysis, publication bias, and interstudy heterogeneity. Results: Twenty-nine studies comprising 3,973 patients with MBC were included. According to our findings, lower ALC was significantly associated with poorer prognosis of OS (HR = 0.57, 95% CI 0.48 to 0.68) and PFS (HR = 0.68, 95% CI 0.58 to 0.79), and greater NLR was associated with poorer OS (HR = 1.50, 95% CI 1.35 to 1.67) and PFS (HR = 1.82, 95% CI 1.42 to 2.35). Furthermore, the prognostic values of ALC and NLR in MBC were also observed in the subgroup analyses regarding cutoff values and ethnicities. Conclusion: Low ALC and elevated NLR were observed to be significantly associated with adverse OS and PFS in MBC, indicating that ALC and NLR may act as potential prognostic biomarkers of MBC patients. Meanwhile, our results will also provide some novel evidence and research clues for the selection and development of clinical treatment strategies for MBC patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021224114.

Cyclin-dependent kinase 2 (CDK2) inhibitors and others novel CDK inhibitors (CDKi) in breast cancer: clinical trials, current impact, and future directions.

Aberrant cyclin-dependent kinase 2 (CDK2) activation has been identified as a main resistance mechanism to CDK4/6 inhibition in hormone-receptor positive (HR+) breast cancer. Additionally, consistent preclinical evidence states its crucial role in MYC and CCNE1 overexpressed cancer survival, such as triple-negative breast cancers (TNBC), thus representing an appealing and relatively unexplored target treatment opportunity. Despite emerging initial results of novel CDK2 inhibitors (CDK2i) activity, a comprehensive outcomes collection is currently absent from the scientific literature. We aim to provide an overview of ongoing clinical trials involving CDK2i in the context of metastatic breast cancer (mBC), either as monotherapy or in combination with other agents. The review extends beyond CDK2i to encompass novel emerging CDK4 inhibitors, combined CDK2/4/6 inhibitors, and the well-known pan-CDK inhibitors including those specifically directed at CDK2. Delving into the results, we critically appraise the observed clinical efficacy and offer valuable insights into their potential impact and future applications.

The exposure to UV filters: Prevalence, effects, possible molecular mechanisms of action and interactions within mixtures.

Substances that can absorb sunlight and harmful UV radiation such as organic UV filters are widely used in cosmetics and other personal care products. Since humans use a wide variety of chemicals for multiple purposes it is common for UV filters to co-occur with other substances either in human originating specimens or in the environment. There is increasing interest in understanding such co-occurrence in form of potential synergy, antagonist, or additive effects of biological systems. This review focuses on the collection of data about the simultaneous occurrence of UV filters oxybenzone (OXYB), ethylexyl-methoxycinnamate (EMC) and 4-methylbenzylidene camphor (4-MBC) as well as other classes of chemicals (such as pesticides, bisphenols, and parabens) to understand better any such interactions considering synergy, additive effect and antagonism. Our analysis identified >20 different confirmed synergies in 11 papers involving 16 compounds. We also highlight pathways (such as transcriptional activation of estrogen receptor, promotion of estradiol synthesis, hypothalamic-pituitary-gonadal (HPG) axis, and upregulation of thyroid-hormone synthesis) and proteins (such as Membrane Associated Progesterone Receptor (MAPR), cytochrome P450, and heat shock protein 70 (Hsp70)) that can act as important key nodes for such potential interactions. This article aims to provide insight into the molecular mechanisms on how commonly used UV filters act and may interact with other chemicals.

Unveiling biological activities of biosynthesized starch/silver-selenium nanocomposite using Cladosporium cladosporioides CBS 174.62.

BACKGROUND AND OBJECTIVES: Microbial cells capability to tolerate the effect of various antimicrobial classes represent a major worldwide health concern. The flexible and multi-components nanocomposites have enhanced physicochemical characters with several improved properties. Thus, different biological activities of biosynthesized starch/silver-selenium nanocomposite (St/Ag-Se NC) were assessed. METHODOLOGY: The St/Ag-Se NC was biosynthesized using Cladosporium cladosporioides CBS 174.62 (C. cladosporioides) strain. The shape and average particle size were investigated using scanning electron microscope (SEM) and high-resolution transmission electron microscope (HR-TEM), respectively. On the other hand, the St/Ag-Se NC effect on two cancer cell lines and red blood cells (RBCs) was evaluated and its hydrogen peroxide (H2O2) scavenging effect was assessed. Moreover, its effects on various microbial species in both planktonic and biofilm growth forms were examined. RESULTS: The St/Ag-Se NC was successfully biosynthesized with oval and spherical shape and a mean particle diameter of 67.87 nm as confirmed by the HR-TEM analysis. St/Ag-Se NC showed promising anticancer activity toward human colorectal carcinoma (HCT-116) and human breast cancer (MCF-7) cell lines where IC50 were 21.37 and 19.98 µg/ml, respectively. Similarly, little effect on RBCs was observed with low nanocomposite concentration. As well, the highest nanocomposite H2O2 scavenging activity (42.84%) was recorded at a concentration of 2 mg/ml. Additionally, Staphylococcus epidermidis (S. epidermidis) ATCC 12,228 and Candida albicans (C. albicans) ATCC 10,231 were the highly affected bacterial and fungal strains with minimum inhibitory concentrations (MICs) of 18.75 and 50 µg/ml, respectively. Moreover, the noticeable effect of St/Ag-Se NC on microbial biofilm was concentration dependent. A high biofilm suppression percentage, 87.5% and 68.05%, were recorded with S. epidermidis and Staphylococcus aureus (S. aureus) when exposed to 1 mg/ml and 0.5 mg/ml, respectively. CONCLUSION: The biosynthesized St/Ag-Se NC showed excellent antioxidant activity, haemocompatibility, and anti-proliferative effect at low concentrations. Also, it exhibited promising antimicrobial and antibiofilm activities.