Metabolic Syndrome and Biotherapeutic Activity of Dairy (Cow and Buffalo) Milk Proteins and Peptides: Fast Food-Induced Obesity Perspective-A Narrative Review.

Metabolic syndrome (MS) is defined by the outcome of interconnected metabolic factors that directly increase the prevalence of obesity and other metabolic diseases. Currently, obesity is considered one of the most relevant topics of discussion because an epidemic heave of the incidence of obesity in both developing and underdeveloped countries has been reached. According to the World Obesity Atlas 2023 report, 38% of the world population are presently either obese or overweight. One of the causes of obesity is an imbalance of energy intake and energy expenditure, where nutritional imbalance due to consumption of high-calorie fast foods play a pivotal role. The dynamic interactions among different risk factors of obesity are highly complex; however, the underpinnings of hyperglycemia and dyslipidemia for obesity incidence are recognized. Fast foods, primarily composed of soluble carbohydrates, non-nutritive artificial sweeteners, saturated fats, and complexes of macronutrients (protein-carbohydrate, starch-lipid, starch-lipid-protein) provide high metabolic calories. Several experimental studies have pointed out that dairy proteins and peptides may modulate the activities of risk factors of obesity. To justify the results precisely, peptides from dairy milk proteins were synthesized under in vitro conditions and their contributions to biomarkers of obesity were assessed. Comprehensive information about the impact of proteins and peptides from dairy milks on fast food-induced obesity is presented in this narrative review article.

Emerging Futuristic Targeted Therapeutics: A Comprising Study Towards a New Era for the Management of TNBC.

Triple-negative breast cancer is characterized by high lethality attributed to factors such as chemoresistance, transcriptomic, and genomic heterogeneity, leading to a poor prognosis and limiting available targeted treatment options. While the identification of molecular targets remains pivotal for therapy involving chemo drugs, the current challenge lies in the poor response rates, low survival rates, and frequent relapses. Despite various clinical investigations exploring molecular targeted therapies in conjunction with conventional chemo treatment, the outcomes have been less than optimal. The critical need for more effective therapies underscores the urgency to discover potent novel treatments, including molecular and immune targets, as well as emerging strategies. This review provides a comprehensive analysis of conventional treatment approaches and explores emerging molecular and immune-targeted therapeutics, elucidating their mechanisms to address the existing obstacles for a more effective management of triple-negative breast cancer.

Microencapsulation of Olive Oil by Dehydration of Emulsion: Effects of the Emulsion Formulation and Dehydration Process.

Microencapsulation of extra virgin olive oil has been taken into consideration. Initially, emulsions were prepared using extra virgin olive oil and aqueous solutions of different proportions of maltodextrin (MD) having dextrose equivalent (DE) 19 and whey protein isolates (WPI), such as 100% MD, 100% WPI, 25% MD + 75% WPI, 50% MD + 50% WPI and 75% MD + 25% WPI. Subsequently, emulsions were used for dehydration by either spray-drying (SD) or freeze-drying (FD) to produce olive oil microcapsules. Emulsion stability, viscosity and droplet size influenced the characteristics of the microcapsules. The highest encapsulation efficiency was achieved using 50% MD + 50% WPI in the emulsions with subsequent SD. The moisture content of the microcapsules increased with increasing proportions of MD. The size of the microcapsules increased with increasing proportions of WPI. The bulk density and tapped density were reduced with higher proportions of MD in the microcapsules. Furthermore, microcapsules with a higher proportion of MD exhibited poor flowability and high cohesiveness. Microcapsules from the higher proportion MD emulsions, followed by SD were spherical with a smooth surface; however, microcapsules with dent structures were produced from 100% WPI in the emulsions with subsequent SD. Microcapsules, produced from emulsions with a higher proportion of WPI, followed by FD were flat flakes and had irregular surfaces.

Theragnostic strategies harnessing the self-renewal pathways of stem-like cells in the acute myeloid leukemia.

Acute myelogenous leukemia (AML) is a genetically heterogeneous and aggressive cancer of the Hematopoietic Stem/progenitor cells. It is distinguished by the uncontrollable clonal growth of malignant myeloid stem cells in the bone marrow, venous blood, and other body tissues. AML is the most predominant of leukemias occurring in adults (25%) and children (15-20%). The relapse after chemotherapy is a major concern in the treatment of AML. The overall 5-year survival rate in young AML patients is about 40-45% whereas in the elderly patients it is less than 10%. Leukemia stem-like cells (LSCs) having the ability to self-renew indefinitely, repopulate and persist longer in the G0/G1 phase play a crucial role in the AML relapse and refractoriness to chemotherapy. Hence, novel treatment strategies and diagnostic biomarkers targeting LSCs are being increasingly investigated. Through this review, we have explored the signaling modulations in the LSCs as the theragnostic targets. The significance of the self-renewal pathways in overcoming the treatment challenges in AML has been highlighted.

Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies.

PURPOSE: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented. METHODS: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling. RESULTS: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only. CONCLUSION: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.

Molecular targets and therapeutics in chemoresistance of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC), which shows immunohistochemically negative expression of hormone receptor i.e., Estrogen receptor and Progesterone receptor along with the absence of Human Epidermal Growth Factor Receptor-2 (HER2/neu). In Indian scenario the prevalence of BC is 26.3%, whereas, in West Bengal the cases are of 18.4%. But the rate of TNBC has increased up to 31% and shows 27% of total BC. Conventional chemotherapy is effective only in the initial stages but with progression of the disease the effectivity gets reduced and shown almost no effect in later or advanced stages of TNBC. Thus, TNBC patients frequently develop resistance and metastasis, due to its peculiar triple-negative nature most of the hormonal therapies also fails. Development of chemoresistance may involve various factors, such as, TNBC heterogeneity, cancer stem cells (CSCs), signaling pathway deregulation, DNA repair mechanism, hypoxia, and other molecular factors. To overcome the challenges to treat TNBC various targets and molecules have been exploited including CSCs modulator, drug efflux transporters, hypoxic factors, apoptotic proteins, and regulatory signaling pathways. Moreover, to improve the targets and efficacy of treatments researchers are emphasizing on targeted therapy for TNBC. In this review, an effort has been made to focus on phenotypic and molecular variations in TNBC along with the role of conventional as well as newly identified pathways and strategies to overcome challenge of chemoresistance.

Antioxidant and Antibacterial Peptides from Soybean Milk through Enzymatic- and Membrane-Based Technologies.

Enzymatic hydrolysis of soybean milk proteins with cysteine protease papain was performed in an advanced bioreactor, operated with batch mode. In soybean milk protein hydrolysis reaction, enzyme and substrate ratio and reaction temperature were varied, ranging from 0.029:100-0.457:100 and 30-60 °C, respectively. The degree of hydrolysis of soybean milk proteins was increased with increase of enzyme and substrate (soybean milk protein) ratio. However, the degree of hydrolysis was increased due to change of reaction temperature from 30 °C to 60 °C with enzyme and substrate ratio 0.229:100 and was reduced when hydrolysis reaction was performed with enzyme and substrate ratio 0.11:100 at hydrolysis temperature 60 °C. Antioxidant capacity of enzyme-treated milk had a similar trend with degree of hydrolysis. In a later exercise, a membrane bioreactor was adopted for continuous production of antioxidant and antibacterial peptides from soybean milk. The membrane bioreactor was operated for 12 h with constant feeding. Ceramic-made tubular membrane with a pore size 20 nm was used. Application of static turbulence promoter in a membrane separation process was investigated and its positive effects, with respect to higher permeate flux and lower energy consumption in filtration process, were proven. Antioxidant capacity and antibacterial activity against Bacillus cereus of enzyme-hydrolyzed milk and permeate from membrane were confirmed.

Biological Activities of Lactose-Derived Prebiotics and Symbiotic with Probiotics on Gastrointestinal System.

Lactose-derived prebiotics provide wide ranges of gastrointestinal comforts. In this review article, the probable biochemical mechanisms through which lactose-derived prebiotics offer positive gastrointestinal health are reported along with the up-to-date results of clinical investigations; this might be the first review article of its kind, to the best of our knowledge. Lactose-derived prebiotics have unique biological and functional values, and they are confirmed as 'safe' by the Food and Drug Administration federal agency. Medical practitioners frequently recommend them as therapeutics as a pure form or combined with dairy-based products (yoghurt, milk and infant formulas) or fruit juices. The biological activities of lactose-derived prebiotics are expressed in the presence of gut microflora, mainly probiotics (Lactobacillus spp. in the small intestine and Bifidobacterium spp. in the large intestine). Clinical investigations reveal that galacto-oligosaccharide reduces the risks of several types of diarrhea (traveler's diarrhea, osmotic diarrhea and Clostridium difficile associated relapsing diarrhea). Lactulose and lactosucrose prevent inflammatory bowel diseases (Crohn's disease and ulcerative colitis). Lactulose and lactitol reduce the risk of hepatic encephalopathy. Furthermore, lactulose, galacto-oligosaccharide and lactitol prevent constipation in individuals of all ages. It is expected that the present review article will receive great attention from medical practitioners and food technologists.