Foaming properties of milk samples collected at various processing stages in a dairy processing factory across two seasons.

BACKGROUND: A foam layer makes an essential contribution to the quality of cappuccino-style drinks. Poor foaming of milk occurs quite often, however, especially in summer. The reasons for this are still unknown. Although a substantial number of studies on the foaming process of milk have been reported, these studies have been laboratory based and have used laboratory or pilot-scale equipment to simulate the processing conditions of a dairy processing factory. This study collected about 40 different samples across different processing stages in a dairy factory over two seasons (two batches per season) and investigated their composition and physical and foaming properties by mechanical mixing and steam injection. RESULTS: The results showed that milk samples collected in summer had a significantly higher content of fat, free fatty acids, and Ca2+ ions, and larger particle sizes but a markedly lower concentration of protein and solid non-fat, and surface tension than the samples collected in spring. These differences provided spring milk with a higher steam injection foamability than summer milk. However, steam injection foam stability, and mechanical mixing foamability and foam stability were not affected by seasonal factors. Milk samples collected in different batches within a season were almost identical with regard to the properties that were investigated. CONCLUSION: The variations in composition and physical properties of milk collected between two seasons could be the reasons for their difference in foamability but not for foam stability. Processes such as standardization, homogenization, and pasteurization improved markedly the foaming properties of milk. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Seroprevalence with epidemiological determinants of hepatitis C virus and Treponema pallidum infection in blood donors of a teaching hospital in southwest Punjab, India: A 5-year study.

Background: A high seroprevalence of various transfusion-transmitted infections (TTIs) in donated blood is the main safety concern, especially in low- and middle-income countries. As per the World Health Organization (WHO) recommendation, all blood donations must be tested for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum infection, and malaria, which mainly comprises the major bulk of TTIs. Aims: The purpose of this study is to observe the seroprevalence of hepatitis C virus and Treponema pallidum infection over the period of 5 years in blood donors of our blood center along with their epidemiological determinants with respect to age, sex, residence, occupation, and type of donors. Materials and Methods: Retrospective study was conducted for the period of 5 years, from 1st January 2017 to December 2021, estimating the seroprevalence of hepatitis C and Treponema pallidum infection in the blood donors along with their epidemiological determinants. Results: Out of 19,689 donations in 5 years, 690 (3.50%) units were positive for transfusion-transmissible infections with 1.67% donors seropositive for HCV, 1.23% for Treponema pallidum infection, 0.42% for HBV, and 0.18% for HIV. The prevalence of TTIs was found to be highest in 2020 (4.52%) and least in 2017 (2.57%). Out of a total of 330 HCV cases detected in 5 years, 84.85% of cases were seen in voluntary donors. Rural donors constituted 71.21% of cases. The majority of cases were seen in the age group of 18-30 years, i.e., 61.82%, and a maximum number of cases were seen in the farmers (31.21%), followed by laborers and construction workers (21.21%). Out of a total of 242 cases of Treponema pallidum infection, 84.29% were seen in voluntary blood donors. Demographic data showed 70.24% of cases in rural donors. Occupational data revealed a maximum number of cases in farmers (34.29%), followed by laborers (21.90%). Conclusion: Higher seroprevalence of HCV and Treponema pallidum infection in our region as compared with other areas is a matter of great concern about the growing infection rate of these in our area. Stringent use of donor selection criteria and more vigorous donor screening is utmost need of the hour for reducing the burden of TTIs in blood transfusion services.

Algorithms for Treating Dyslipidemia in Youth.

PURPOSE OF REVIEW: The goal of this article is to review algorithms for treating dyslipidemia in youth, discuss pitfalls, propose enhanced algorithms to address pitfalls, and consider future directions. RECENT FINDINGS: The presence of modifiable and non-modifiable cardiovascular disease (CVD) risk factors during childhood is associated with CVD-related events in adulthood. Recent data has shown that childhood initiation of statin therapy in youth < 18 years of age with familial hypercholesterolemia reduces the risk of adult CVD. However, pediatric dyslipidemia remains undertreated in part due to a lack of primary health care providers with adequate understanding of screening guidelines and pediatric lipidologists with experience in treatment and follow-up of this unique population. Management algorithms have been published by the National Heart, Lung, and Blood Institute and American Heart Association as tools to empower clinicians to manage dyslipidemia. We propose enhanced algorithms, which incorporate recently approved pharmacotherapy to address the management gaps. Future algorithms based upon clinical risk scores may enhance treatment and improve outcomes. Algorithms for dyslipidemia management which target youth < 18 years of age are tools which empower clinicians to manage dyslipidemia in this unique population. Enhanced algorithms may help address pitfalls. We acknowledge the need for further risk assessment tools in pediatrics for tailored dyslipidemia management.

Influence of minerals on the foaming properties of milk.

A comprehensive study on the effect of mineral content on milk foaming properties was conducted. Samples with increased mineral concentration were prepared by adding four different types of minerals (KH2PO4, K3Cit, CaCl2 and MgCl2) at three different concentration levels (5, 10 and 20 mM) in both reconstituted skim milk powder and milk protein concentrate. Samples with reduced minerals were prepared by reconstituting milk protein concentrate in modified simulated milk ultrafiltrates. Different mineral types showed different effects on the physicochemical properties of milk samples. The addition of K3Cit increased the viscosity and decreased the surface tension while there were no significant differences between the samples added with KH2PO4, MgCl2, or CaCl2. In terms of foaming properties, the addition of CaCl2 or MgCl2 significantly increased the foam strength and stability while decreasing foamability. In contrast, the addition of K3Cit significantly decreased foam stability and foam strength while increasing foamability. It was also found that reduction in minerals in the range studied did not affect the foaming properties of milk. These results indicate that the effect of minerals on milk foaming properties depends on the type of mineral and the concentration. This provides an insight that while designing dairy-based food products, the mineral content can be manipulated to achieve the desired foaming properties.

Effect of shearing-induced lipolysis on foaming properties of milk.

BACKGROUND: The attraction of cappuccino-style beverages is attributed to the foam layer, as it greatly improves the texture, appearance, and taste of these products. Typical milk has a low concentration of free fatty acids (FFAs), but their concentration can increase due to lipolysis during processing and storage, which is detrimental to the foamability and foam stability of milk. There are contradictory results in reported studies concerning the effects of FFAs on the foaming properties of milk due to differences in milk sources, methods inducing lipolysis, and methods of creating foam. In this study, the foaming properties and foam structure of milk samples whose lipolysis was induced by ultra-turraxing, homogenisation, and microfluidisation (1.5-3.5 µ-equiv. mL-1 FFAs) were investigated. RESULTS: Compared with others, microfluidised milk samples had the smallest particle size, lowest absolute zeta potential, and highest surface tension; thus exhibited high foamability and foam stability, and very small and homogeneous air bubbles in foam structure. For all shearing methods, increasing FFA content from 1.5 to 3.5 µ-equiv. mL-1 markedly decreased the surface tension, foamability, and foam stability of milk samples. The FFA level that led to undesirable foam structure was 1.5 µ-equiv. mL-1 for ultra-turraxed milk samples and 2.5 µ-equiv. mL-1 for homogenised and microfluidised ones. CONCLUSION: Shearing-induced lipolysis greatly affected the physical properties of milk samples and subsequently their foaming properties and foam structure. At the same FFA level, lipolysis induced by microfluidisation was much less detrimental to the foaming properties of milk than lipolysis induced by ultra-turraxing and homogenisation. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Advances in pulsed electric stimuli as a physical method for treating liquid foods.

There is a need for alternative technologies that can deliver safe and nutritious foods at lower costs as compared to conventional processes. Pulsed electric field (PEF) technology has been utilised for a plethora of different applications in the life and physical sciences, such as gene/drug delivery in medicine and extraction of bioactive compounds in food science and technology. PEF technology for treating liquid foods involves engineering principles to develop the equipment, and quantitative biochemistry and microbiology techniques to validate the process. There are numerous challenges to address for its application in liquid foods such as the 5-log pathogen reduction target in food safety, maintaining the food quality, and scale up of this physical approach for industrial integration. Here, we present the engineering principles associated with pulsed electric fields, related inactivation models of microorganisms, electroporation and electropermeabilization theory, to increase the quality and safety of liquid foods; including water, milk, beer, wine, fruit juices, cider, and liquid eggs. Ultimately, we discuss the outlook of the field and emphasise research gaps.

Protein Nanoparticles for Enhanced Oral Delivery of Coenzyme-Q10: in Vitro and in Silico Studies.

Coenzyme-Q10 (CoQ10) is a hydrophobic benzoquinone with antioxidant and anti-inflammatory properties. It is known to reduce oxidative stress in various health conditions. However, due to the low solubility, permeability, stability, and poor oral bioavailability, the oral dose of CoQ10 required for the desired therapeutic effect is very high. In the present study, CoQ10 is encapsulated into two milk derived proteins ß-lactoglobulin and lactoferrin (BLG and LF) to produce self-assembled nanostructures of around 100-300 nm with high encapsulation efficiency (5-10% w/w). Both CoQ10-BLG and CoQ10-LF nanoparticles (NPs) significantly improved the aqueous solubility of CoQ10 60-fold and 300-fold, compared to CoQ10 alone, which hardly dissolves in water. Insight into the difference in solubility enhancement between BLG and LF was obtained using in silico modeling, which predicted that LF possesses multiple prospective CoQ10 binding sites, potentially enabling greater loading of CoQ10 on LF compared to BLG, which was predicted to be less capable of binding CoQ10. At pH 7.4, CoQ10-LF NPs showed a burst release between 30 min and 2 h then plateaued at 12 h with 30% of the total drug released over 48 h. However, pure CoQ10-BLG and pure CoQ10 had a significantly lower release rate with less than 15% and 8% cumulative release in 48 h, respectively. Most importantly, both BLG and LF NPs significantly improved CoQ10 permeability compared to the pre-dissolved drug across the Caco-2 monolayer with up to 2.5-fold apparent permeability enhancement for CoQ10-LF─further confirming the utility of this nanoencapsulation approach. Finally, in murine macrophage cells (J774A.1), CoQ10-LF NPs displayed significantly higher anti-ROS properties compared to CoQ10 (predissolved in DMSO) without affecting the cell viability. This study paves the way in improving oral bioavailability of poorly soluble drugs and nutraceuticals using milk-based self-assembled nanoparticles.

Nanosecond pulsed electric field treatment of human milk: Effects on microbiological inactivation, whey proteome and bioactive protein.

In the current study, nanosecond pulsed electric field (nsPEF) was investigated at lab-scale to optimise processing conditions of donor human milk to reduce bacterial counts, and to evaluate its effect on the bioactive proteins in human milk. Response surface methodology was utilized to optimise critical processing parameters. Two optimal nsPEF processing conditions were validated: 15 kV voltage, 6000 pulses at 20 Hz frequency, and 15 kV voltage, 6000 pulses at 50 Hz frequency. Compared to raw human milk, nsPEF processed milk had over 60 % retention of lysozyme, lactoperoxidase and lactoferrin, and 100 % retention of xanthine oxidase and immunoglobulin A. The contents of the five proteins were significantly higher after nsPEF processing when compared with Holder pasteurization. Liquid chromatography-mass spectrometry analysis showed that loss of milk proteins was smaller for samples treated with nsPEF than Holder pasteurization. These results indicated that nsPEF is a promising novel pasteurization method.

Update on management of paediatric dyslipidaemia.

PURPOSE OF REVIEW: Atherosclerosis and associated cardiovascular risk factors originate in childhood; hence, early management of dyslipidaemia is vital. However, hypercholesterolemia remains untreated or undertreated in many youths. We review current therapies, drugs under investigation and consider potential future directions for the management of paediatric dyslipidaemia to highlight the recent evidence and new therapeutic options for future use. RECENT FINDINGS: Cardiovascular disease (CVD) risk factors in childhood, including dyslipidaemia, are associated with CVD risk and clinical CVD events in adulthood. Recent data show that initiation of statin therapy in childhood in children with familial hypercholesterolemia reduces the risk of CVD in adulthood. Several well tolerated and efficacious treatment options have become available in recent times for the management of dyslipidaemia in youth. Many new lipid-lowering drugs are under investigation to widen the available choices. Some of these drugs are now available for use in paediatrics, while some remain targets for future use. SUMMARY: We review available treatment options for paediatric dyslipidaemia management, discuss potential limitations and propose future directions. We also acknowledge the need for continued research in paediatrics for optimal paediatric dyslipidaemia management.

Current Cannabidiol Safety: A Review.

BACKGROUND: Marijuana, also known as cannabis, is the second most widely used illegal psychoactive substance smoked worldwide after tobacco, mainly due to the psychoactive effects induced by D-9-tetrahydrocannabinol (9-THC). Cannabidiol (CBD) is extracted from cannabis and may be used as an anti-inflammatory agent. Some patents on cannabidiol are discussed in this review. The cannabinoid is a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC); and is available in several administration modes, most known as CBD oil. OBJECTIVES: This study aims to provide an enhanced review of cannabidiol properties used in treating inflammation. This review also emphasises the current safety profile of cannabidiol. METHODS: Cannabis is also called Marijuana. It is the second most commonly used illegal psychoactive substance in the universe after tobacco. D-9-tetrahydrocannabinol (9-THC) present in cannabis produces psychoactive effects. Cannabidiol (CBD) extracted from cannabis is used for antiinflammatory purposes. Cannabis smoking causes various types of cancer, such as lung, tongue, and jaw. The current review took literature from Google Scholar, PubMed, and Google Patents. Many clinical investigations are included in this review. RESULT: After analysing the literature on cannabis, it has been suggested that although cannabis is banned in some countries, it may be included in the treatment and mitigation of some diseases and symptoms like pain management, epilepsy, cancer, and anxiety disorder. Mild side effects were frequently observed in cannabis medications, which included infertility in females, liver damage, etc. Conclusion: Cannabis contains chemical compounds such as the cannabinoids delta-9- tetrahydrocannabinol (THC), a psychoactive substance, and non-psychoactive cannabidiol (CBD). Cannabidiol has been confirmed as an efficient treatment of epilepsy in several clinical trials, with one pure CBD product named Epidiolex. It is also used in treating anxiety and acne, as a pain reliever, and has anti-inflammatory properties.

The Results of Different Heating Temperatures on Activities of Bioactive Proteins in Human Milk.

BACKGROUND: The most utilized pasteurization method in donor human milk banks is Holder pasteurization (heating 62.5 °C for 30 min). However, many bioactive proteins are heat sensitive and are inactivated. RESEARCH AIM: To determine the results of a range of heating regimes on the activities of xanthine oxidase, lactoperoxidase and lysozyme, the concentrations of immunoglobulin A and lactoferrin, as well as bacterial inactivation. METHOD: This prospective, cross-sectional, intervention study was designed to measure the influence of heating temperatures on bioactive components in donor human milk. Milk samples were processed at 40, 50, 55, 62.5, 75, 127 °C and the activities of the enzymes, and the concentration of immune proteins, were measured. RESULTS: No bacterial colonies were detectable, using standard culture methods, after heating above 50 ºC. All proteins studied retained over 60% concentrations or activities when the pasteurization temperature was 50 ºC or lower, while their concentrations or activities were lost at higher temperatures. For lactoferrin, the residual concentration was above 80% when heating temperature was under 55 °C, while only 20% remained after Holder pasteurization. Both xanthine oxidase and lactoperoxidase had little residual activity when temperatures were above Holder pasteurization. Lysozyme retained a greater proportion of residual activity than other proteins, following heating at all temperatures. CONCLUSIONS: The concentrations or activities of immune proteins and bioactive enzymes decreased when heated above 50 °C. The results of this study can be used to design temperature control guidance during alternative methods of pasteurization.

Comparative proteomic analysis of donor human milk pasteurized by hydrostatic high-pressure.

The aim of this study was to comprehensively investigate the effect of Holder pasteurization (HoP) compared with that of hydrostatic high-pressure (HHP) processing on human milk proteins, including milk fat globule membrane (MFGM) proteins, whey proteins and caseins. Milk fat globules in milk processed by high-pressure were similar to those in raw milk in terms of their size distribution and microstructure, while the globules in milk processed by HoP were aggregated. The protein profiles of milk subjected to HHP processing more closely resembled those of raw milk than HoP milk. Proteins in milk whey were less affected by HoP or HHP than MFGM and casein proteins. The findings indicated a better preservation of the protein profile for HHP compared to HoP of human milk.

The Assessment of Serum Fibronectin Levels as a Potential Biomarker for the Severity of Drug-Sensitive Pulmonary Tuberculosis: A Pilot Study.

BACKGROUND: Tuberculosis (TB) is a global health burden caused by Mycobacterium tuberculosis (Mtb) infection. Fibronectin (Fn) facilitates Mtb attachment to host cells. We studied the Fn levels in smear-positive TB patients to assess its correlation with disease severity based on sputum smears and chest X-rays. METHODS: Newly detected consecutive sputum AFB-positive pulmonary TB patients (n = 78) and healthy control subjects (n = 11) were included. The mycobacterial load in the sputum smear was assessed by IUATLD classification, ranging from 0 to 3. The severity of pulmonary involvement was assessed radiologically in terms of both the number of zones involved (0-6) and as localized (up to 2 zones), moderate (3-4 zones), or extensive (5-6 zones). The serum human fibronectin levels were measured by using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Catalogue No: CK-bio-11486, Shanghai Coon Koon Biotech Co., Ltd., Shanghai, China). RESULTS: The PTB patients showed lower Fn levels (102.4 ± 26.7) compared with the controls (108.8 ± 6.8), but they were not statistically significant. Higher AFB smear grades had lower Fn levels. The chest X-ray zones involved were inversely correlated with Fn levels. The Fn levels, adjusted for age and gender, decreased with increased mycobacterial load and the number of chest radiograph zones affected. A Fn level <109.39 g/mL predicted greater TB severity (sensitivity of 67.57% and specificity of 90.38%), while a level <99.32 pg/mL predicted severity based on the chest radiology (sensitivity of 84.21% and specificity of 100%). CONCLUSIONS: The Fn levels are lower in tuberculosis patients and are negatively correlated with severity based on sputum mycobacterial load and chest radiographs. The Fn levels may serve as a potential biomarker for assessing TB severity, which could have implications for early diagnosis and treatment monitoring.

Continuous flow fabrication of green graphene oxide in aqueous hydrogen peroxide.

Highly processible graphene oxide (GO) has a diversity of applications as a material readily dispersed in aqueous media. However, methods for preparing such free-standing GO use hazardous and toxic reagents and generate significant waste streams. This is an impediment for uptake of GO in any application, for developing sustainable technologies and industries, and overcoming this remains a major challenge. We have developed a robust scalable continuous flow method for fabricating GO directly from graphite in 30% aqueous hydrogen peroxide which dramatically minimises the generation of waste. The process features the continuous flow thin film microfluidic vortex fluidic device (VFD), operating at specific conditions while irradiated sequentially by UV LED than a NIR pulsed laser. The resulting 'green' graphene oxide (gGO) has unique properties, possessing highly oxidized edges with large intact sp2 domains which gives rise to exceptional electrical and optical properties, including purple to deep blue emission of narrow full width at half maximum (<35 nm). Colloidally stable gGO exhibits cytotoxicity owing to the oxidised surface groups while solid-state films of gGO are biocompatible. The continuous flow method of generating gGO also provides unprecedented control of the level of oxidation and its location in the exfoliated graphene sheets by harnessing the high shear topological fluid flows in the liquid, and varying the wavelength, power and pulse frequency of the light source.

The Sin3A/MAD1 Complex, through Its PAH2 Domain, Acts as a Second Repressor of Retinoic Acid Receptor Beta Expression in Breast Cancer Cells.

Retinoids are essential in balancing proliferation, differentiation and apoptosis, and they exert their effects through retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RARß is a tumor-suppressor gene silenced by epigenetic mechanisms such as DNA methylation in breast, cervical and non-small cell lung cancers. An increased expression of RARß has been associated with improved breast cancer-specific survival. The PAH2 domain of the scaffold protein SIN3A interacts with the specific Sin3 Interaction Domain (SID) of several transcription factors, such as MAD1, bringing chromatin-modifying proteins such as histone deacetylases, and it targets chromatin for specific modifications. Previously, we have established that blocking the PAH2-mediated Sin3A interaction with SID-containing proteins using SID peptides or small molecule inhibitors (SMI) increased RARß expression and induced retinoic acid metabolism in breast cancer cells, both in in vitro and in vivo models. Here, we report studies designed to understand the mechanistic basis of RARß induction and function. Using human breast cancer cells transfected with MAD1 SID or treated with the MAD SID peptide, we observed a dissociation of MAD1, RARα and RARß from Sin3A in a coimmunoprecipitation assay. This was associated with increased RARα and RARß expression and function by a luciferase assay, which was enhanced by the addition of AM580, a specific RARα agonist; EMSA showed that MAD1 binds to E-Box, similar to MYC, on the RARß promoter, which showed a reduced enrichment of Sin3A and HDAC1 by ChIP and was required for the AM580-enhanced RARß activation in MAD1/SID cells. These data suggest that the Sin3A/HDAC1/2 complex co-operates with the classical repressors in regulating RARß expression. These data suggest that SIN3A/MAD1 acts as a second RARß repressor and may be involved in fine-tuning retinoid sensitivity.

Camel milk: A review of its nutritional value, heat stability, and potential food products.

Camel milk is superior to bovine milk and quite close to human milk in terms of its nutritional value. It contains high concentrations of many bioactive compounds that are essential for human health. Despite its profound nutritional and health benefits, food products produced from camel milk are still very limited compared to bovine milk. Differences in the composition of bovine and camel milk make the production processes for bovine milk products unsuitable for camel milk products. Therefore, a comprehensive understanding regarding the composition, bioactive compounds, and the heat stability of camel milk is essential to preserve the inherent nutritional value of camel milk while achieving desirable attributes in the final products. In this review, the properties and functionalities of macro-nutrients in camel milk, especially heat stability of camel milk and its proteins are described. In addition, technical aspects of the production of various camel milk products, including difficulties in their production and directions for further research to enhance their quality, are comprehensively discussed.

Physicochemical Properties and Whey Proteomes of Camel Milk Powders Produced by Different Concentration and Dehydration Processes.

Camel milk powder production is an alternative to preserve the perishable milk for later-date consumption. However, the impacts of dehydration processes on bioactive compounds in camel milk are largely unknown. Hence, the present study attempted to compare the physicochemical properties and protein profiles of camel milk powders produced by different concentration and dehydration processes. Six camel milk powders were produced by freeze- and spray-drying methods in conjunction with two liquid concentration techniques, namely spray dewatering and reverse osmosis. The results of proteomic analysis showed that direct freeze-dried camel milk powder had the least changes in protein profile, followed by direct spray-dried powder. The camel milk powders that underwent concentration processes had more profound changes in their protein profiles. Among the bioactive proteins identified, lactotransferrin and oxidase/peroxidase had the most significant decreases in concentration following processing. On the contrary, glycosylation-dependent cell adhesion molecule 1, peptidoglycan recognition protein 1, and osteopontin increased in concentration. The results revealed that direct freeze drying was the most ideal method for preserving the bioactive proteins during camel milk powder production. However, the freeze-drying technique has cost and scalability constraints, and the current spray-drying technique needs improvement to better retain the bioactivity of camel milk during powder processing.

Comprehensive biochemical and proteomic characterization of seasonal Australian camel milk.

Although camel milk is increasingly becoming a popular alternative to bovine milk around the world including Australia, studies of Australian camel milk are still lacking. A comprehensive and systematic analysis of major nutritional components, physical properties, antimicrobial enzymes and whey proteomes of Australian camel milk obtained over four seasons was conducted, for the first time in present study. The composition and physical properties of Australian camel milk varied with season, milking frequency and yield. The highest lactoperoxidase and polyamine oxidase activity was observed in summer and winter, respectively. A total of 97 proteins were quantified, on a relative basis, across all the seasonal bulk milk samples. Summer camel milk contained higher amounts of functional whey proteins, such as lactotransferrin, peptidoglycan recognition protein 1, osteopontin and lactoperoxidase. These results contribute to a better understanding of the Australian camel milk and provide insights into processing of dairy products from this milk.

Invasive phenotype in triple negative breast cancer is inhibited by blocking SIN3A-PF1 interaction through KLF9 mediated repression of ITGA6 and ITGB1.

SIN3A, a scaffold protein has regulatory functions in tumor biology. Through its Paired amphipathic helix (PAH2) domain, SIN3A interacts with PHF12 (PF1), a protein with SIN3 interaction domain (SID) that forms a complex with MRG15 and KDM5A/B. These components are often overexpressed in cancer. In the present study, we evaluated the role of SIN3A and its interacting partner PF1 in mediating inhibition of tumor growth and invasion in triple negative breast cancer (TNBC). We found profound inhibition of invasion, migration, and induction of cellular senescence by specific disruption of the PF1/SIN3A PAH2 domain interaction in TNBC cells expressing PF1-SID transcript or peptide treatment. Genome-wide transcriptomic analysis by RNA-seq revealed that PF1-SID downregulates several gene sets and pathways linked to invasion and migration. Integrin α6 (ITGA6) and integrin ß1 (ITGB1) and their downstream target proteins were downregulated in PF1-SID cells. We further determined increased presence of SIN3A and transcriptional repressor, KLF9, on promoters of ITGA6 and ITGB1 in PF1-SID cells. Knockdown of KLF9 leads to re-expression of ITGA6 and ITGB1 and restoration of the invasive phenotype, functionally linking KLF9 to this process. Overall, these data demonstrate that specific disruption of PF1/SIN3A, inhibits tumor growth, migration, and invasion. Also, PF1-SID not only inhibits tumor growth by senescence induction and reduced proliferation, but it also targets cancer stem cell gene expression and blocks mammosphere formation. Overall, these data demonstrate a mechanism whereby invasion and metastasis of TNBC can be suppressed by inhibiting SIN3A-PF1 interaction and enhancing KLF9 mediated suppression of ITGA6 and ITGB1.

Comparison of milk fat globule membrane and whey proteome between Dromedary and Bactrian camel.

Camel milk is rich in nutrients and its impact on human medicine and nutrition cannot be ignored. We conducted an in-depth analysis of milk proteins obtained from two camel breed (Camelus bactrianus, CB and Camelus dromedarius, CD). Label-free proteomic technology was performed to analysis the MFGM and whey proteomes of CB and CD milk. In total, 1133 MFGM proteins and 627 whey proteins were identified from camel milk. Results revealed that 216 MFGM proteins and 109 whey proteins were significantly different between them. In addition, the cellular process, cell and binding were the predominately GO annotations of milk proteins. KEGG analysis shown that most proteins were involved in metabolic pathways. Furthermore, many proteins were found to be involved in PI3K/AKT signaling pathway, which could be the possible reason for hypoglycemic effect of camel milk. These results could provide a further understanding for unique biological characteristics of camel milk proteins.