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Fungal infections present a significant health risk, particularly in immunocompromised individuals. Berberine, a natural isoquinoline alkaloid, has demonstrated broad-spectrum antimicrobial activity, though its antifungal potential and underlying mechanisms against both yeast-like and filamentous fungi are not fully understood. This study investigates the antifungal efficacy of berberine against Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, and Trichophyton mentagrophytes in vitro, as well as its therapeutic potential in a murine model of cryptococcal infection. Berberine showed strong antifungal activity, with MIC values ranging from 64 to 128 µg/mL. SEM and TEM analyses revealed that berberine induced notable disruptions to the cell wall and membrane in C. neoformans. No signs of cell necrosis or apoptosis were observed in fungal cells treated with 2 × MIC berberine, and it did not increase intracellular ROS levels or affect mitochondrial membrane potential. Molecular docking and binding affinity assays demonstrated a strong interaction between berberine and the fungal enzyme CYP51, with a dissociation constant (KD) of less than 1 × 10−12 M, suggesting potent inhibition of ergosterol biosynthesis. In vivo studies further showed that berberine promoted healing in guinea pigs infected with T. mentagrophytes, and in a murine cryptococcal infection model, it prolonged survival and reduced lung inflammation, showing comparable efficacy to fluconazole. These findings indicate that berberine exerts broad-spectrum antifungal effects through membrane disruption and CYP51 inhibition, highlighting its potential as a promising therapeutic option for fungal infections.

Objective: To evaluate the antifungal activity of coptisine, isolated from Coptis chinensis, against Cryptococcus neoformans both in vitro and in vivo, along with investigating its underlying mechanism. Methods: Microbroth dilution assay and disk diffusion assay were used to evaluate the antifungal activity of coptisine in vitro. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) was performed to observe the changes induced by coptisine in the morphology and structural integrity of C. neoformans cells. Flow cytometry was utilized for the analysis of cell apoptosis. To examine if apoptosis induced by coptisine includes initial mitochondrial impairment, changes in Δψm were assessed using flow cytometry with Rhodamine-123. Additionally, reactive oxygen species levels were identified through both confocal microscopy and flow cytometry. Furthermore, the therapeutic efficacy of coptisine in vivo was evaluated employing a murine model of C. neoformans infection induced by cyclophosphamide. Results: Coptisine has demonstrated significant antifungal efficacy against C. neoformans, exhibiting a half minimum inhibitory concentration (MIC50) of 61.64 µg/mL. SEM and TEM has unveiled that coptisine provokes significant alterations in morphology and structural integrity of C. neoformans cells, such as the formation of extensive cellular debris, compromised cell walls, and membrane distortions. Experimental data further elucidate that coptisine disrupts the cell membrane, encompassing the cytoplasmic membrane, culminating in the accumulation of reactive oxygen species, ultimately triggering cell apoptosis. Further, coptisine significantly improved the survival of infected mice, and reduced the damage caused by C. neoformans to the visceral tissues of infected mice. Conclusions: This study underscores the promising potential of coptisine, a natural alkaloid, as a prospective candidate for the development of an antifungal agent.

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.

Objective: Herpes simplex virus type 1 (HSV-1) is a worldwide pathogen and mainly puts immunocompromised patients at higher risk of various complications. This research aims to demonstrate the antiviral activity of chelerythrine (CHE), an alkaloid compound derived from the traditional Chinese medicine Mcleaya cordata, towards the HSV-1 F strain. Methods: Bioassay-guided fractionation was carried out in order to isolate the antiviral compound CHE. The plaque reduction assay was used to evaluate the antiviral activity of CHE. The combination of quantitative PCR (qPCR) and western blot was used to elucidate whether CHE interferes with viral DNA synthesis, followed by time-of-addition assay to examine which steps of HSV-1 infection CHE affected. The immunofluorescent assay and transmission electron microscopy assay were performed to further analyze the intracellular localization and the ultrastructural features of HSV-1 virions with the treatment of CHE. The binding affinity in CHE to targeted viral glycoprotein was investigated by surface plasmon resonance (SPR) assay and docking simulation. Results: CHE displayed a significant antiviral effect against HSV-1 at 0.312 to 2.5 µM with a viral titer reduction of 29.38% to 61.02%. CHE had an EC50 value of 1.78 µM against HSV-1, and the selectivity index (SI) for CHE was 4.07. Additionally, CHE inhibits ICP0 expression in the immediate early stage of infection, which further affected the early stage of infection, and subsequent viral replication. Results of the SPR assay showed that CHE had strong-binding affinity to gB with a KD value of 7.80 × 107 M, while gD with a value of 1.18 × 106 M. TEM revealed that CHE can clearly inhibit the virion release. In silico experiments further confirmed that CHE had low binding free energy in the activity sites of gB and gD. Conclusion: This study revealed that CHE directly targeted viral gB or gD as a potent glycoprotein inhibitor, which suggested that CHE could be a virus entry inhibitor for HSV-1 treatment.

During the previous few years, the relationship between the gut microbiota, metabolic disorders, and diet has come to light, especially due to the understanding of the mechanisms that particularly link the gut microbiota with obesity in animal models and clinical trials. Research has led to the understanding that the responses of individuals to dietary inputs vary remarkably therefore no single diet can be suggested to every individual. The variations are attributed to differences in the microbiome and host characteristics. In general, it is believed that the immanent nature of host-derived factors makes them difficult to modulate. However, diet can more easily shape the microbiome, potentially influencing human physiology through modulation of digestion, absorption, mucosal immune response, and the availability of bioactive compounds. Thus, diet could be useful to influence the physiology of the host, as well as to ameliorate various disorders. In the present study, we have described recent developments in understanding the disparities of gut microbiota populations between individuals and the primary role of diet-microbiota interactions in modulating human physiology. A deeper understanding of these relationships can be useful for proposing personalized nutrition strategies and nutrition-based therapeutic interventions to improve human health.

Chia (S. hispanica L.) is an annual herbaceous plant that has gained popularity for its seeds of high-quality vegetative proteins, richest contents of omega-3 polyunsaturated fatty acids (Ω-3 PUFA), soluble dietary fiber, and great gelling ability, as well as its high contents of bioactive peptides of antioxidative and nutraceutical potential for many other clinical biomarkers. Such health protective bioactive peptides should be utilized for supplementation in the food and nutrition industries. This review was therefore designed to align the researches done on chia bioactive peptide’s derivation, processing, consumption and to identify their antioxidative and nutraceutical potential for various disease biomarkers. The evidence gathered is fairly compelling for the health-promising nutraceutical and clinical potential of chia seed bioactive peptides as antioxidants, dipeptidyl peptidase-IV inhibitors (DPP4), angiotensin-converting enzyme (ACE) inhibitors, and anti-inflammatory drugs. Their assimilation into everyday diets has the potential to open new doors in health departments and food sectors.

Refined sugar is a processed product containing 99% sucrose, which is obtained from sugarcane (70%) or sugar beet (30%). In modern societies, sugar continues to play a significant role in the diet, recognised not only for its flavour and special sweetening properties but also for its role in food preservation. On the other hand, a high consumption of refined sugar is associated with non-communicable diseases and many health issues such as a high risk of dental caries, overweight and neurodevelopmental disorders in children. Alternatives like unrefined sugars have generated a lot of interest as a healthy substitute due to their nutraceutical properties. This paper is aimed to review the beneficial effects of sugar derived from natural sources and highlight health problems that could be caused by refined processed sugar. Refined sugar is frequently used in variety of items including processed foods, soft drinks or ice creams although it is considered unhealthy due to its high salt and sugar content as well as added fats and artificial coloring. Natural sugars are preferred because they have a high nutritional value and a high concentration of healthy compounds, which offset the negative effects of refined sugar. Therefore, removing refined sugar or at least reducing its consumption should be promoted as a healthier option in food choices.

In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.

Streptomyces are factories of antimicrobial secondary metabolites. We isolated a Streptomyces species associated with the Pelargonium graveolens rhizosphere. Its total metabolic extract exhibited potent antibacterial and antifungal properties against all the tested pathogenic microbes. Whole genome sequencing and genome analyses were performed to take a look at its main characteristics and to reconstruct the metabolic pathways that can be associated with biotechnologically useful traits. AntiSMASH was used to identify the secondary metabolite gene clusters. In addition, we searched for known genes associated with plant growth-promoting characteristics. Finally, a comparative and pan-genome analysis with three closely related genomes was conducted. It was identified as Streptomyces vinaceusdrappus strain AC-40. Genome mining indicated the presence of several secondary metabolite gene clusters. Some of them are identical or homologs to gene clusters of known metabolites with antimicrobial, antioxidant, and other bioactivities. It also showed the presence of several genes related to plant growth promotion traits. The comparative genome analysis indicated that at least five of these gene clusters are highly conserved through rochei group genomes. The genotypic and phenotypic characteristics of S. vinaceusdrappus strain AC-40 indicate that it is a promising source of beneficial secondary metabolites with pharmaceutical and biotechnological applications.

Bovine mastitis (BM) is one of the most common diseases of dairy cattle, causing economic and welfare problems in dairy farming worldwide. Because of the predominant bacterial etiology, the treatment of BM is mostly based on antibiotics. However, the antimicrobial resistance (AMR), treatment effectiveness, and the cost of mastitis at farm level are linked to limitations in the antibiotic therapy. These scenarios have prompted the quest for new preventive options, probiotics being one interesting alternative. This review article sought to provide an overview of the recent advances in the use of probiotics for the prevention and treatment of BM. The cellular and molecular interactions of beneficial microbes with mammary gland (MG) cells and the impact of these interactions in the immune responses to infections are revised. While most research has demonstrated that some probiotics strains can suppress mammary pathogens by competitive exclusion or the production of antimicrobial compounds, recent evidence suggest that other probiotic strains have a remarkable ability to modulate the response of MG to Toll-like receptor (TLR)-mediated inflammation. Immunomodulatory probiotics or immunobiotics can modulate the expression of negative regulators of TLR signaling in the MG epithelium, regulating the expression of pro-inflammatory cytokines and chemokines induced upon pathogen challenge. The scientific evidence revised here indicates that immunobiotics can have a beneficial role in MG immunobiology and therefore they can be used as a preventive strategy for the management of BM and AMR, the enhancement of animal and human health, and the improvement of dairy cow milk production.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has stressed the global health system to a significant level, which has not only resulted in high morbidity and mortality but also poses a threat for future pandemics. This situation warrants efforts to develop novel therapeutics to manage SARS-CoV-2 in specific and other emerging viruses in general. This study focuses on SARS-CoV2 RNA-dependent RNA polymerase (RdRp) mutations collected from Saudi Arabia and their impact on protein structure and function. The Saudi SARS-CoV-2 RdRp sequences were compared with the reference Wuhan, China RdRp using a variety of computational and biophysics-based approaches. The results revealed that three mutations—A97V, P323I and Y606C—may affect protein stability, and hence the relationship of protein structure to function. The apo wild RdRp is more dynamically stable with compact secondary structure elements compared to the mutants. Further, the wild type showed stable conformational dynamics and interaction network to remdesivir. The net binding energy of wild-type RdRp with remdesivir is -50.76 kcal/mol, which is more stable than the mutants. The findings of the current study might deliver useful information regarding therapeutic development against the mutant RdRp, which may further furnish our understanding of SARS-CoV-2 biology.

Epithelial ovarian cancer (EOC) is one of the deadliest reproductive tract malignancies that form on the external tissue covering of an ovary. Cassia fistula is popular for its anti-inflammatory and anticarcinogenic properties in conventional medications. Nevertheless, its molecular mechanisms are still unclear. The current study evaluated the potential of C. fistula for the treatment of EOC using network pharmacology approach integrated with molecular docking. Eight active constituents of C. fistula were obtained from two independent databases and the literature, and their targets were retrieved from the SwissTargetPrediction. In total, 1077 EOC associated genes were retrieved from DisGeNET and GeneCardsSuite databases, and 800 potential targets of eight active constituents of C. fistula were mapped to the 1077 EOC targets and intersected targets from two databases. Ultimately, 98 potential targets were found from C. fistula for EOC. Finally, the protein–protein interaction network (PPI) topological interpretation revealed AKT1, CTNNB1, ESR1, and CASP3 as key targets. This is the first time four genes have been found against EOC from C. fistula. The major enriched pathways of these candidate genes were established by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) investigations. To confirm the network pharmacology findings, the molecular docking approach demonstrated that active molecules have higher affinity for binding to putative targets for EOC suppression. More pharmacological and clinical research is required for the development of a drug to treat EOC.

Spirulina (Arthrospira platensis) has been consumed by humans since ancient times. It is rich in high added-value compounds such as chlorophylls, carotenoids and polyphenols. Pulsed electric fields (PEF) is an innovative non-thermal technique that improves the extraction of bioactive compounds from diverse sources. PEF pre-treatment (3 kV/cm, 100 kJ/kg) combined with supplementary extraction with binary solvents at different times was evaluated to obtain the optimal conditions for extraction. In addition, the results obtained were compared with conventional treatment (without PEF pre-treatment and constant shaking) and different strains of Spirulina from diverse geographical locations. The optimal extraction conditions for recovering the bioactive compounds were obtained after applying PEF treatment combined with the binary mixture EtOH/H2O for 180 min. The recovery of total phenolic content (TPC) (19.76 ± 0.50 mg/g DM (dry matter) and carotenoids (0.50 ± 0.01 mg/g DM) was more efficient in the Spirulina from Spain. On the other hand, there was a higher recovery of chlorophylls in the Spirulina from China. The highest extraction of total antioxidant compounds was in Spirulina from Costa Rica. These results show that PEF, solvents and the condition of growing affect the extraction of antioxidant bioactive compounds from Spirulina. The combination of PEF and EtOH/H2O is a promising technology due to its environmental sustainability.

Beneficial microbes with immunomodulatory capacities (immunobiotics) and their non-viable forms (postimmunobiotics) could be effectively utilized in formulations towards the prevention of respiratory viral infections. In this study, novel immunobiotic strains with the ability to increase antiviral immunity in porcine alveolar macrophages were selected from a library of Lactobacillus gasseri. Postimmunobiotics derived from the most remarkable strains were also evaluated in their capacity to modulate the immune response triggered by Toll-like receptor 3 (TLR3) in alveolar macrophages and to differentially regulate TLR3-mediated antiviral respiratory immunity in infant mice. We provide evidence that porcine alveolar macrophages (3D4/31 cells) are a useful in vitro tool for the screening of new antiviral immunobiotics and postimmunobiotics by assessing their ability to modulate the expression IFN-β, IFN-λ1, RNAseL, Mx2, and IL-6, which can be used as prospective biomarkers. We also demonstrate that the postimmunobiotics derived from the Lactobacillus gasseri TMT36, TMT39 and TMT40 (HK36, HK39 or HK40) strains modulate the innate antiviral immune response of alveolar macrophages and reduce lung inflammatory damage triggered by TLR3 activation in vivo. Although our findings should be deepened and expanded, the results of the present work provide a scientific rationale for the use of nasally administered HK36, HK39 or HK40 to beneficially modulate TLR3-triggerd respiratory innate immune response.

The interest in the therapeutic use of probiotic microorganisms has been increased during the last decade although the doubts have ascended about the probiotics mainly because their beneficial effects are not fully understood, and, in many cases, their usefulness has not been validated in clinical trials. Consequently, the notion got a considerable interest in those strains having proven probiotic potential to be engineered for improvement in their beneficial features. The process of genetic engineering can also be used for probiotic strains for the reversion of antimicrobial resistance and other modifications for their safer and effective human applications. The lactic acid bacilli are predominantly opposite as they already have gained attention owing to their health-promoting benefits and their safety for human consumption; therefore, their use, especially as a delivery agent of vaccines and drugs, is gaining attention. The tailoring of probiotic strains will not only improve the data regarding the probiotic potential of these strains but also clinch the doubts concerning these probiotics. This article focuses on the approaches of bioengineered probiotics and discusses the potential prospects for their therapeutic applications including immunomodulation, cognitive health, and anticancer therapeutics.

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.

COVID-19 remains a deadly disease that poses a serious threat to humanity. COVID-19 vaccines protect the public and limit viral spread. However, public acceptance is significantly dependent on the efficacy and side effects (SEs) of the vaccinations being produced. Four important mechanisms have been examined for COVID-19 vaccines: DNA-based, mRNA-based, protein-based, and inactivated viruses. Vaccination safety research was formerly limited to manufacturer-sponsored studies, but numerous additional cross-sectional survey-based studies conducted globally have contributed to the generation of vaccine-related safety data reports. Twenty-seven studies and twenty-four case reports published-up till 2021 were overviewed for the presentation of SEs and their severity. Injection site pain remained the most dominant localized SE, while headache and fatigue were the most prevalent systemic SEs. Most studies reported that all vaccinations were safe, with very little or no adverse effects, but the nature of SEs was reported to be more persistent in DNA- and mRNA-based vaccines, while inactivated viral vaccines were associated with longer-duration SEs. Overall, SEs were found to be more dominant in women and youngsters. Case reports of adverse reactions have also been documented, but there is still a need to find out their pathological linkage with the COVID-19 vaccination.

Over the past decade, the use of probiotics as feed supplements in animal production has increased considerably due to the ban on antibiotic growth promoters in livestock. This review provides an overview of the current situation, limitation, and prospects for probiotic formulations applied to livestock. Recently, the use of probiotics in livestock has been suggested to significantly improve their health, immunity, growth performance, nutritional digestibility, and intestinal microbial balance. Furthermore, it was reported that the use of probiotics in animals was helpful in equilibrating their beneficial microbial population and microbial turnover via stimulating the host immune response through specific secretions and competitive exclusion of potentially pathogenic bacteria in the digestive tract. Recently, there has been great interest in the understanding of probiotics targeted diet and its ability to compete with harmful microbes and acquire their niches. Therefore, the present review explores the most commonly used probiotic formulations in livestock feed and their effect on animal health. In summary, this article provides an in-depth knowledge about the formulation of probiotics as a step toward a better alternative to antibiotic healthy growth strategies.

Previous studies have reported that recombinant tumor necrosis factor (TNF)-α has powerful antiviral activity but severe systematic side effects. Jasminin is a common bioactive component found in Chinese herbal medicine beverage “Jasmine Tea”. Here, we report that jasminin-induced endogenous TNF-α showed antiviral activity in vitro. The underlying TNF-α-inducing action of jasminin was also investigated in RAW264.7 cells. The level of endogenous TNF-α stimulated by jasminin was first analyzed by an enzyme-linked immunosorbent assay (ELISA) from the cell culture supernatant of RAW264.7 cells. The supernatants were then collected to investigate the potential antiviral effect against herpes simplex virus 1 (HSV-1). The antiviral effects of jasminin alone or its supernatants were evaluated by a plaque reduction assay. The potential activation of the PI3K–Akt pathway, three main mitogen-activated protein kinases (MAPKs), and nuclear factor (NF)–κB signaling pathways that induce TNF-α production were also investigated. Jasminin induces TNF-α protein expression in RAW264.7 cells without additional stimuli 10-fold more than the control. No significant up-expression of type I, II, and III interferons; interleukins 2 and 10; nor TNF-β were observed by the jasminin stimuli. The supernatants, containing jasminin-induced-TNF-α, showed antiviral activity against HSV-1. The jasminin-stimulated cells caused the simultaneous activation of the Akt, MAPKs, and NF–κB signal pathways. Furthermore, the pretreatment of the cells with the Akt, MAPKs, and NF–κB inhibitors effectively suppressed jasminin-induced TNF-α production. Our research provides evidence that endogenous TNF-α can be used as a strategy to encounter viral infections. Additionally, the Akt, MAPKs, and NF–κB signaling pathways are involved in the TNF-α synthesis that induced by jasminin.

Dietary components have an important role on the structure and function of host gut microbial communities. Even though, various dietary components, such as carbohydrates, fats, proteins, fibers, and vitamins, have been studied in depth for their effect on gut microbiomes, little attention has been paid regarding the impact of several food antioxidants on the gut microbiome. The long-term exposure to reactive oxygen species (ROS) can cause microbial dysbiosis which leads to numerous intestinal diseases such as microbiota dysbiosis, intestinal injury, colorectal cancers, enteric infections, and inflammatory bowel diseases. Recently, it has been shown that the food derived antioxidant compounds might protect the host from intestinal oxidative stress via modulating the composition of beneficial microbial species in the gut. The present review summarizes the impact of food antioxidants including antioxidant vitamins, dietary polyphenols, carotenoids, and bioactive peptides on the structure as well as function of host gut microbial communities. Several in vitro, animal model, and clinical studies indicates that food antioxidants might modify the host gut microbial communities and their health status. However, still further clarification is needed as to whether changes in certain microbial species caused by food additives may lead to changes in metabolism and immune function.

The search for waste minimization and the valorization of by-products are key to good management and improved sustainability in the food industry. The great production of almonds, based on their high nutritional value as food, especially almond kernels, generates tons of waste yearly. The remaining parts (skin, shell, hulls, etc.) are still little explored, even though they have been used as fuel by burning or as livestock feed. The interest in these by-products has been increasing, as they possess beneficial properties, caused by the presence of different bioactive compounds, and can be used as promising sources of new ingredients for the food, cosmetic and pharmaceutical industry. Additionally, the use of almond by-products is being increasingly applied for the fortification of already-existing food products, but there are some limitations, including the presence of allergens and mycotoxins that harden their applicability. This review focuses on the extraction technologies applied to the valorization of almond by-products for the development of new value-added products that would contribute to the reduction of environmental impact and an improvement in the sustainability and competitiveness of the almond industry.

A substantial amount of emerging research is indicating that the gut microbiota has a significant impact on human health. Alterations of gut microbiota have clear consequences on intestinal homeostasis, physiology, gut microbiome, immune system and host metabolic pathways. Diet composition plays an important role in the control of gut microbial populations and, thus, in the prevention, management and treatment of certain diseases such as cancer, diabetes. A comprehensive analysis of previously reported results revealed that the gut microbiota can be modulated by diet and the composition of gut microbiota can be influenced by various diet components. The symbiotic relationship between different gut microbial communities regulates the immune system and, therefore, any dysbiosis can dysregulate the immune system. Further research is needed to fully understand the mechanisms involved in the interactions between diet composition, gut microbiota and associated diseases.

The exopolysaccharide (EPS) from Lactobacilli play a vital part in their probiotic action; on the other hand, up to date, there is little data exist about the effect of EPS on cancer. The aim of the current study is the EPS isolation produced by Lactobacillus kefiri MSR101 (MSR101 EPS) and examination of structural characteristics as well as their capability to prevent the colon cancer (HT-29) cells growth. For the first time, the structure of EPS from Lactobacillus kefiri MSR101 is identified, which is heteropolysaccharide with a repeating unit containing glucose and galactose. The FT-IR and NMR analysis of MSR101 EPS indicates the occurrence of carboxyl, hydroxyl groups, respectively. The XRD results indicated that the MSR101 EPS has partial crystalline nature. SEM and AFM micrographs revealed an extremely spongy structure which suggests that the MSR101 EPS has plasticized film features. Furthermore, the in-vitro anticancer activity results suggested that the newly isolated MSR101 EPS (400 µg/ml) had satisfactory anticancer action on HT-29 cancerous cells (44.1%) and up-regulate the expression of Cyto-c, BAX, BAD, caspase3, caspase8, and caspase9. In general, the present results suggested that the exopolysaccharide from Lactobacillus kefiri MSR101 not only used in the functional food product but also considered as a topical medication due to their effectiveness against colon cancer.

Lactobacillus delbrueckii subsp. delbrueckii TUA4408L is able to differentially modulate the innate immune response of porcine intestinal epithelial cells triggered by TLR4 activation. This strain also has a remarkable ability to grow on plant substrates. These two immunological and biotechnological characteristics prompted us to evaluate whether the soymilk by-product okara fermented with the TUA4408L strain can serve as an immunobiotic feed with the ability to beneficially modulate the intestinal immunity of piglets after weaning to improve their productivity. Our in vivo studies demonstrated that the administration of immunobiotic TUA4408L-fermented okara feed significantly increased piglet growth performance and meat quality. These positive effects were associated with the ability of the TUA4408L-fermented okara feed to beneficially modulate both intestinal microbiota and immunity in pigs. The immunobiotic feed improved the abundance of the beneficial bacteria Lactobacillus and Lactococcus in the gut of pigs, reduced blood markers of inflammation, and differentially regulated the expression of inflammatory and regulatory cytokines in the intestinal mucosa. These findings indicate that the immunobiotic TUA4408L-fermented okara feed could be an economical and environmentally friendly option to improve the growth performance and immune health of pigs.