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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis (CRS) characterized by the presence of nasal polyps (NP) in the paranasal mucosa. Despite the complex etiology, NP is believed to result from chronic inflammation. The long-term aftermath of the type 2 response is responsible for symptoms seen in NP patients, i.e. rhinorrhea, hyposmia, and nasal obstruction. Immune cellular tolerogenic mechanisms, particularly CD4 + Foxp3 + regulatory T cells (Tregs), are crucial to curtail inflammatory responses. Current evidence suggests impaired Treg activity is the main reason underlying the compromise of self-tolerance, contributing to the onset of CRSwNP. There is compelling evidence that tumor necrosis factor 2 (TNFR2) is preferentially expressed by Tregs, and TNFR2 is able to identify the most potent suppressive subset of Tregs. Tumor necrosis factor (TNF)-TNFR2 interaction plays a decisive role in the activation and expansion of Tregs. This review summarizes current understanding of Tregs biology, focusing on the discussion of the recent advances in the study of TNF-TNFR2 axis in the upregulation of Treg function as a negative feedback mechanism in the control of chronic inflammation. The role of dysregulation of Tregs in the immunopathogenesis of CRSwNP will be analyzed. The future perspective on the harnessing Tregs-mediated self-tolerant mechanism in the management of CRSwNP will be introduced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied., Aim: To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats., Methods: The rats were grouped as follows ( n = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated., Results: On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant., Conclusion: The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model., Competing Interests: Conflict-of-interest statement: All the authors declare no conflict of interest in conducting this research., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Mesoporous silica nanoparticles (MSNs) have great potential for applications as a drug delivery system (DDS) due to their unique properties such as large pore size, high surface area, biocompatibility, biodegradability, and stable aqueous dispersion. The MSN-mediated DDS can carry chemotherapeutic agents, optical sensors, photothermal agents, short interfering RNA (siRNA), and gene therapeutic agents. The MSN-assisted imaging techniques are applicable in cancer diagnosis. However, their synthesis via a chemical route requires toxic chemicals and is challenging, time-consuming, and energy-intensive, making the process expensive and non-viable. Fortunately, nature has provided a viable alternative material in the form of biosilica from marine resources. In this review, the applications of biosilica nanoparticles synthesized from marine diatoms in the field of drug delivery, biosensing, imaging agents, and regenerative medicine, are highlighted. Insights into the use of biosilica in the field of DDSs are elaborated, with a focus on different strategies to improve the physico-chemical properties with regards to drug loading and release efficiency, targeted delivery, and site-specific binding capacity by surface functionalization. The limitations, as well as the future scope to develop them as potential drug delivery vehicles and imaging agents, in the overall therapeutic management, are discussed.

Purpose: The Breast Imaging Reporting and Data System (BI-RADS) lexicon used in reporting breast imaging has several categories with specific positive predictive values for breast cancer. Among those, BI-RADS 4 is associated with a wider range of risk for breast cancer, which makes the decision for biopsy difficult. The study aim was to determine the malignancy rate and clinical outcomes of BI-RADS 4 lesions in Hospital Universiti Sains Malaysia (HUSM) for a period of five years., Methods: This was a retrospective study of patients diagnosed by mammographic or ultrasonographic findings with BI-RADS 4 breast lesions in HUSM, Kelantan from July 2015 to June 2020. Data were collected from the medical records and an electronic database. Patients with BI-RADS 4 lesions who underwent biopsy and had a known tissue diagnosis were included in this study. The data was used to calculate the malignancy rate and associated positive predictive factors for breast cancer associated with BI-RADS 4 lesions., Results: From the mammography and ultrasonography performed at HUSM from July 2015 to June 2020, a total of 256 lesions were categorized as BI-RADS 4. However, only 198 BI-RADS 4 lesions underwent biopsy and were included in the study. Of these 198 lesions, 26.8% were malignant on histopathological examination of the biopsy samples. Simple logistic regression analysis showed that age, diabetes mellitus, hypertension, number of parity, and certain mammogram findings were significantly associated with breast cancer. Invasive breast cancer was the most common type. Fibrocystic disease was the most common benign pathology, followed by fibroadenoma., Conclusion: The malignancy rate of BI-RADS 4 lesions in HUSM was similar to previously reported rates. A thorough evaluation of positive predictive factors and careful selection of patients for biopsy in BI-RADS 4 lesions will minimize unwanted biopsies and associated patient anxiety, in addition to reducing the health care burden., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Marthay et al.)

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Aggressive tissue biopsy is commonly unavoidable in the management of most suspected tumor cases to conclusively verify the presence of cancerous cells through histological assessment. The extracted tissue is also immunostained for detection of antigens (tissue tumor markers) of potential prognostic or therapeutic importance to assist in treatment decision. Although liquid biopsies can be a powerful tool for monitoring treatment response, they are still excluded from standard cancer diagnostics, and their utility is still being debated in the scientific community. With a myriad of soluble tissue tumor markers now being discovered, liquid biopsies could completely change the current paradigms of cancer management. Recently, soluble programmed cell death ligand-1 (sPD-L1), which is found in the peripheral blood, i.e. serum and plasma, has shown potential as a pre-therapeutic predictive marker as well as a prognostic biomarker to monitor treatment efficacy. Thus, this review focuses on the emergence of sPD-L1 and promising technologies for its detection in order to support liquid biopsies for future cancer management., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.

Triple-negative breast cancer (TNBC) is an aggressive breast type of cancer with no expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). It is a highly metastasized, heterogeneous disease that accounts for 10-15% of total breast cancer cases with a poor prognosis and high relapse rate within five years after treatment compared to non-TNBC cases. The diagnostic and subtyping of TNBC tumors are essential to determine the treatment alternatives and establish personalized, targeted medications for every TNBC individual. Currently, TNBC is diagnosed via a two-step procedure of imaging and immunohistochemistry (IHC), which are operator-dependent and potentially time-consuming. Therefore, there is a crucial need for the development of rapid and advanced technologies to enhance the diagnostic efficiency of TNBC. This review discusses the overview of breast cancer with emphasis on TNBC subtypes and the current diagnostic approaches of TNBC along with its challenges. Most importantly, we have presented several promising strategies that can be utilized as future TNBC diagnostic modalities and simultaneously enhance the efficacy of TNBC diagnostic.

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib., Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis., Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring., Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment., .

Background: Vascular endothelial growth factor receptors (VEGFRs) are major endothelial growth factor receptors that influence the growth of a tumor. Microvessel density., (: MVD) is the quantification method of various aspects of tumor vasculature that indicates angiogenic activity. This study aims to analyze the correlation between MVD to the expression of VEGFRs on breast cancer tissue., Materials and Method: A total of 60 N-methyl-N-nitrosourea (MNU)-induced breast carcinomas in rats were suppressed by using antiangiogenic drugs. The rats were then sacrificed, and the tumor was fixed in 10% formalin, paraffin embedded, and immunohistochemistry stained using VEGFRs and CD34., Result: One-way ANOVA test showed a significant difference in all markers that have been used (P < 0.05) on MNU-breast tumor treated with rapamycin (M= 90.1664, SD= 7.4487), PF4 (M= 93.7946, SD= 7.1303) and rapamycin + PF4 (M= 93.6990, SD= 1.8432). We obtained a significant reduction of MVD count on breast carcinoma for rapamycin group (M= 25.6786, SD= 9.7075) and rapamycin + PF4 group (M= 30.5250, SD= 13.6928) while PF4 group (M=47.7985, SD=4.8892) showed slightly increase compared to control (M= 45.1875, SD= 4.4786). There was a moderately strong, positive correlation between angiogenic markers; Flt-1 (r= 0.544, n=60, P < 0.005) and Flt-4 (r= 0.555, n= 60, P < 0.005) while Flk-1 (r= 0.797, n= 60, P < 0.005) showed a strong, positive correlation with MVD., Conclusion: MVD was strongly correlated to the VEGFRs expression on breast carcinoma.