Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus).

The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.

A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes.

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.

The Combined Effect of Licorice Extract and Bone Marrow Mesenchymal Stem Cells on Cisplatin-Induced Hepatocellular Damage in Rats.

Drug-induced liver damage is a life-threatening disorder, and one major form of it is the hepatotoxicity induced by the drug cisplatin. In folk medicine, Licorice (Glycyrrhiza glabra (is used for detoxification and is believed to be a potent antioxidant. Currently, the magically self-renewable potential of bone marrow mesenchymal stem cells (BM-MSCs) has prompted us to explore their hepatoregenerative capability. The impact of G. glabra extract (GGE) and BM-MSCs alone and, in combination, on protecting against hepatotoxicity was tested on cisplatin-induced liver injury in rats. Hepatic damage, as revealed by liver histopathology and increased levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA), was elevated in rats by received 7 mg/kg of cisplatin intraperitoneally. The combination of GGE and BM-MSCs returned the enzyme levels to near the normal range. It also improved levels of liver superoxide dismutase (SOD) and glutathione (GSH) and reduced MDA levels. Additionally, it was found that when GGE and BM-MSCs were used together, they significantly downregulated caspase9 (Casp9), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), and interleukin-1ß (IL-1ß), which are involved in severe proinflammatory and apoptotic signaling cascades in the liver. Moreover, combining GGE and BM-MSCs led to the normal result of hepatocytes in several examined liver histological sections. Therefore, our findings suggest that GGE may have protective effects against oxidative liver damage and the promising regenerative potential of BM-MSCs.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis.

Sentinel lymph node (SLN) sampling is important for evaluating the nodal stage of breast cancer when the axillary nodes are clinically free of metastasis. The intraoperative frozen section (IFS) of SLN is used for lymph node assessment. This meta-analysis aims to provide evidence about the diagnostic accuracy and the applicability of IFS of SLN in breast cancer patients. Data were collected by searching PubMed, Cochrane, Scopus, and Web of Science electronic databases for trials matching our eligibility criteria. The statistical analysis included the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and pooled studies' diagnostic odds ratio outcomes. The analyses were conducted using the Open Meta-analyst software. This meta-analysis pooled the results of 110 studies. The overall sensitivity of IFS for SLN metastasis was 74.7%; 95% CI [72.0, 77.2], P < 0.001. It was 31.4% 95% CI [25.2, 38.3], P < 0.001 for the micro-metastasis, and 90.2%; 95% CI [86.5, 93.0], P < 0.001 for the macro-metastasis. The overall specificity was 99.4%; 95% CI [99.2, 99.6], P < 0.001. The overall positive likelihood ratio was 121.4; 95% CI [87.9, 167.6], P < 0.001, and the overall negative likelihood ratio was 0.226; 95% CI [0.186, 0.274], P < 0.001. The overall diagnostic odds ratio of IFS for diagnosing SLN metastasis was 569.5; 95% CI [404.2, 802.4], P < 0.001. The intraoperative frozen section of SLN has good sensitivity for diagnosing breast cancer macro-metastasis. However, the sensitivity is low for micro-metastasis. The specificity is very satisfactory.

A flavonoid-rich fraction of Monolluma quadrangula inhibits xanthine oxidase and ameliorates potassium oxonate-induced hyperuricemia in rats.

Hyperuricemia represents a risk factor for the progression of chronic kidney disease. Oxidative stress and inflammation are implicated in the mechanisms underlying hyperuricemia-mediated kidney injury. Monolluma quadrangula possesses several beneficial effects; however, its effect on hyperuricemia has not been investigated. This study evaluated the renoprotective and xanthine oxidase (XO) inhibitory activity of M. quadrangula in hyperuricemic rats. Phytochemical investigation revealed the presence of six known flavonoid isolated for the first time from this species. The rats received M. quadrangula extract (MQE) and potassium oxonate (PO) for 7 days. In vitro assays showed the radical scavenging and XO inhibitory activities of MQE, and in silico molecular docking revealed the inhibitory activity of the isolated flavonoids towards XO. Hyperuricemic rats showed elevated serum uric acid, creatinine, urea, and XO activity, and renal pro-inflammatory cytokines, MDA and NO, and decreased GSH, SOD, and catalase. MQE ameliorated serum uric acid, urea, creatinine, and XO activity, and renal pro-inflammatory cytokines. In addition, MQE attenuated renal oxidative stress, enhanced antioxidants, downregulated URAT-1, and GLUT-9 and upregulated OAT-1 in PO-induced rats. In conclusion, M. quadrangula attenuated hyperuricemia and kidney impairment by suppressing XO activity, oxidative stress and inflammation, and modulating urate transporters.

MXene (Ti3C2Tx)-Embedded Nanocomposite Hydrogels for Biomedical Applications: A Review.

Polymeric nanocomposites have been outstanding functional materials and have garnered immense attention as sustainable materials to address multi-disciplinary problems. MXenes have emerged as a newer class of 2D materials that produce metallic conductivity upon interaction with hydrophilic species, and their delamination affords monolayer nanoplatelets of a thickness of about one nm and a side size in the micrometer range. Delaminated MXene has a high aspect ratio, making it an alluring nanofiller for multifunctional polymer nanocomposites. Herein, we have classified and discussed the structure, properties and application of major polysaccharide-based electroactive hydrogels (hyaluronic acid (HA), alginate sodium (SA), chitosan (CS) and cellulose) in biomedical applications, starting with the brief historical account of MXene's development followed by successive discussions on the synthesis methods, structures and properties of nanocomposites encompassing polysaccharides and MXenes, including their biomedical applications, cytotoxicity and biocompatibility aspects. Finally, the MXenes and their utility in the biomedical arena is deliberated with an eye on potential opportunities and challenges anticipated for them in the future, thus promoting their multifaceted applications.

Bioactive-Based Cosmeceuticals: An Update on Emerging Trends.

Cosmetic-containing herbals are a cosmetic that has or is claimed to have medicinal properties, with bioactive ingredients purported to have medical benefits. There are no legal requirements to prove that these products live up to their claims. The name is a combination of "cosmetics" and "pharmaceuticals". "Nutricosmetics" are related dietary supplements or food or beverage products with additives that are marketed as having medical benefits that affect appearance. Cosmetic-containing herbals are topical cosmetic-pharmaceutical hybrids intended to enhance the health and beauty of the skin. Cosmetic-containing herbals improve appearance by delivering essential nutrients to the skin. Several herbal products, such as cosmetic-containing herbals, are available. The present review highlights the use of natural products in cosmetic-containing herbals, as natural products have many curative effects as well as healing effects on skin and hair growth with minimal to no side effects. A brief description is given on such plants, their used parts, active ingredients, and the therapeutic properties associated with them. Mainly, the utilization of phytoconstituents as cosmetic-containing herbals in the care of skin and hair, such as dryness of skin, acne, eczema, inflammation of the skin, aging, hair growth, and dandruff, along with natural ingredients, such as for hair colorant, are explained in detail in the present review.

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1ß, interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.

Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges.

In this focused progress review, the most widely accepted methods of transdermal drug delivery are hypodermic needles, transdermal patches and topical creams. However, microneedles (MNs) (or microneedle arrays) are low-invasive 3D biomedical constructs that bypass the skin barrier and produce systemic and localized pharmacological effects. In the past, biomaterials such as carbohydrates, due to their physicochemical properties, have been extensively used to manufacture microneedles (MNs). Due to their wide range of functional groups, carbohydrates enable the design and development of tunable properties and functionalities. In recent years, numerous microneedle products have emerged on the market, although much research needs to be undertaken to overcome the various challenges before the successful introduction of microneedles into the market. As a result, carbohydrate-based microarrays have a high potential to achieve a future step in sensing, drug delivery, and biologics restitution. In this review, a comprehensive overview of carbohydrates such as hyaluronic acid, chitin, chitosan, chondroitin sulfate, cellulose and starch is discussed systematically. It also discusses the various drug delivery strategies and mechanical properties of biomaterial-based MNs, the progress made so far in the clinical translation of carbohydrate-based MNs, and the promotional opportunities for their commercialization. In conclusion, the article summarizes the future perspectives of carbohydrate-based MNs, which are considered as the new class of topical drug delivery systems.

Therapeutic promise of carotenoids as antioxidants and anti-inflammatory agents in neurodegenerative disorders.

Neurodegenerative disorders (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis have various disease-specific causal factors and pathological features. A very common characteristic of NDs is oxidative stress (OS), which takes place due to the elevated generation of reactive oxygen species during the progression of NDs. Furthermore, the pathological condition of NDs including an increased level of protein aggregates can further lead to chronic inflammation because of the microglial activation. Carotenoids (CTs) are naturally occurring pigments that play a significant role in averting brain disorders. More than 750 CTs are present in nature, and they are widely available in plants, microorganisms, and animals. CTs are accountable for the red, yellow, and orange pigments in several animals and plants, and these colors usually indicate various types of CTs. CTs exert various bioactive properties because of its characteristic structure, including anti-inflammatory and antioxidant properties. Due to the protective properties of CTs, levels of CTs in the human body have been markedly linked with the prevention and treatment of multiple diseases including NDs. In this review, we have summarized the relationship between OS, neuroinflammation, and NDs. In addition, we have also particularly focused on the antioxidants and anti-inflammatory properties of CTs in the management of NDs.

Spirulina platensis protects against microcystin-LR-induced toxicity in rats.

Microcystis aeruginosa produces an abundant cyanotoxin (microcystins (MCs) in freshwater supplies. MCs have adverse health hazards to animals and humans. Microcystin-leucine-arginine (microcystin-LR or MC-LR) is the most studied among these MCs due to their high toxicity. So, this study was designed to evaluate the possible therapeutic role of the natural algal food supplement, Spirulina platensis (SP), against MC-LR-induced toxic effects in male Wistar rats. Forty rats were randomly divided into five groups. Control and SP groups orally administered distilled water and SP (1000 mg/kg/daily), respectively, for 21 days. MC-LR group was intraperitoneally injected with MC-LR (10 µg/kg/day) for 14 days. MC-LR-SP500 and MC-LR-SP1000 groups were orally treated with SP (500 and 1000 mg/kg, respectively) for 7 days and concomitantly with MC-LR for 14 days. MC-LR induced oxidative hepatorenal damage, cardiotoxicity, and neurotoxicity greatly, which was represented by reduction of reduced glutathione content and the activities of glutathione peroxidase, catalase, and superoxide dismutase and elevation of concentrations of nitric oxide and malondialdehyde in renal, hepatic, brain, and heart tissues. In addition, it increased serum levels of urea, creatinine, tumor necrosis factor-alfa, interleukin-1beta and interleukin-6 and serum activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB. However, S. platensis restored normal levels of measured serum parameters, ameliorated MC-LR-induced oxidative damage, and normalized tissue antioxidant biomarkers. In conclusion, SP alleviated MC-induced organ toxicities by mitigating oxidative and nitrosative stress and lipid peroxidation.

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders.

Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications.

BACKGROUND: Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. METHODS: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. RESULTS: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. CONCLUSION: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.

Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats.

Hepatocellular carcinoma (HCC) is one of the world's most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly diabetes mellitus (DM) and insulin resistance, are important risk factors for the advancement of HCC. Recently, retrospective studies showed that metformin (MET) could protect the hepatic tissues in pre-existing diabetes mellitus from HCC. The purpose of this study was to assess the role of MET treatment in the pre-existing diabetic rats before and after HCC induction by diethylnitrosamine (DEN). Thirty-five male Sprague Dawley albino rats were partitioned into the following groups: Group 1 (Gp1) was the control. Gp2 was injected intraperitoneally (i.p) with streptozotocin (STZ) (80 mg/kg) and DEN (50 mg/kg/7 weeks). Gp3, Gp4, and Gp5 were injected as in Gp2 and treated with MET (150 mg/kg) before and/or after HCC induction. Biochemical parameters including liver functions, lipid profile, and oxidative stress biomarkers were determined. Furthermore, histological and immunohistochemical changes were assessed in all groups. Our results illustrated that the group of rats that were treated with STZ and DEN had significant changes in both liver functions and were associated with alterations in the liver histopathological architectures. Treatment with MET before or after HCC induction ameliorated the cellular changes in the liver tissues; however, the utmost protection was found in a group of rats, which were treated with MET before and after HCC induction.

Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications

Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. Methods: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. Results: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. Conclusion: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.(AU)

Proteomic analysis of Red Sea Conus taeniatus venom reveals potential biological applications

Abstract Background: Diverse and unique bioactive neurotoxins known as conopeptides or conotoxins are produced by venomous marine cone snails. Currently, these small and stable molecules are of great importance as research tools and platforms for discovering new drugs and therapeutics. Therefore, the characterization of Conus venom is of great significance, especially for poorly studied species. Methods: In this study, we used bioanalytical techniques to determine the venom profile and emphasize the functional composition of conopeptides in Conus taeniatus, a neglected worm-hunting cone snail. Results: The proteomic analysis revealed that 84.0% of the venom proteins were between 500 and 4,000 Da, and 16.0% were > 4,000 Da. In C. taeniatus venom, 234 peptide fragments were identified and classified as conotoxin precursors or non-conotoxin proteins. In this process, 153 conotoxin precursors were identified and matched to 23 conotoxin precursors and hormone superfamilies. Notably, the four conotoxin superfamilies T (22.87%), O1 (17.65%), M (13.1%) and O2 (9.8%) were the most abundant peptides in C. taeniatus venom, accounting for 63.40% of the total conotoxin diversity. On the other hand, 48 non-conotoxin proteins were identified in the venom of C. taeniatus. Moreover, several possibly biologically active peptide matches were identified, and putative applications of the peptides were assigned. Conclusion: Our study showed that the composition of the C. taeniatus-derived proteome is comparable to that of other Conus species and contains an effective mix of toxins, ionic channel inhibitors and antimicrobials. Additionally, it provides a guidepost for identifying novel conopeptides from the venom of C. taeniatus and discovering conopeptides of potential pharmaceutical importance.

Evaluation of Bifidobacteria and Lactobacillus Probiotics as Alternative Therapy for Salmonella typhimurium Infection in Broiler Chickens.

Chicken Salmonella enterica serovars are enteric bacteria associated with massive public health risks and economic losses. There is a widespread antimicrobial resistance among S. enterica serotypes, and innovative solutions to antibiotic resistance are needed. We aimed to use probiotics to reduce antibiotic resistance and identify the major probiotic players that modify the early interactions between S. enterica and host cells. One-day-old cobb broiler chicks were challenged with S. typhimurium after oral inoculation with different probiotic strains for 3 days. The adherence of different probiotic strains to Caco-2 intestinal epithelial cells was studied in vitro. Lactobacillus (Lacticaseibacillus) casei ATTC334 and Bifidobacterium breve JCM1192 strains attached to Caco-2 cells stronger than B. infantis BL2416. L. casei ATTC334 and B. breve JCM1192 reduced S. typhimurium recovery from the cecal tonsils by competitive exclusion mechanism. Although B. infantis BL2416 bound poorly to Caco-2 epithelial cells, it reduced S. typhimurium recovery and increased IFN-γ and TNF-α production. L. casei ATTC334, B. breve JCM1192 and B. infantis BL2416 improved body weight gain and the food conversion rate in S. typhimurium-infected broilers. B. longum Ncc2785 neither attached to epithelial cells nor induced IFN-γ and TNF-α release and consequently did not prevent S. typhimurium colonization in broiler chickens. In conclusion, probiotics prevented the intestinal colonization of S. typhimurium in infected chickens by competitive exclusion or cytokine production mechanisms.

Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats.

Dyslipidemia is a risk factor for cardiovascular disease, steatohepatitis, and progression of liver disorders. This study investigated the protective effect of farnesol (FAR), a sesquiterpene alcohol, against liver injury in high cholesterol diet (HCD)-fed rats, and its modulatory effect on fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). HCD was supplemented for 10 weeks, and the rats were concurrently treated with FAR. Rats that received HCD exhibited significant elevation of serum cholesterol, triacylglycerols, LDL and vLDL cholesterol, CRP, and pro-inflammatory cytokines and increased values of the cardiovascular risk indices. Serum transaminases, ALP, LDH and CK-MB, and hepatic lipid peroxidation (LPO), cholesterol, and triacylglycerols were increased in HCD-fed rats. Treatment with FAR greatly ameliorated dyslipidemia and liver function, reduced inflammatory mediators, LPO, and hepatic lipid infiltration and enhanced anti-oxidant defenses. FAR suppressed hepatic FAS, ACC, and SREPB-1c mRNA abundance and FAS activity in HDC-fed rats. In addition, molecular docking simulations pinpointed the binding modes of FAR to the active pocket residues of FAS and ACC. In conclusion, FAR possesses a strong anti-hyperlipidemic/anti-hypercholesterolemic activity mediated through its ability to modulate hepatic FAS, ACC, and SREPB-1c. FAR prevented oxidative stress, inflammation, and liver injury induced by HCD. Thus, FAR may represent a promising lipid-lowering agent that can protect against dyslipidemia and its linked metabolic deregulations.

Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPARγ and Nrf2/HO-1 signaling.

Chicoric acid (CA) is a natural antioxidant with promising hepatoprotective activity. We investigated the potential of CA to prevent methotrexate (MTX) hepatotoxicity, pointing to the role of Nrf2/HO-1 signaling and PPARγ. Rats received CA for 15 days and were then injected with MTX at day 16. Blood and tissue samples were collected for analysis at day 19. CA ameliorated liver function markers and mitigated histological alterations in MTX-induced rats. Pre-treatment with CA suppressed reactive oxygen species and lipid peroxidation and enhanced antioxidants in MTX-induced rats. Moreover, CA upregulated hepatic Nrf2, HO-1, NQO-1, and PPARγ, and attenuated inflammation. Consequently, CA inhibited apoptosis by increasing Bcl-2 expression and suppressing Bax, cytochrome c, and caspase-3 in MTX-administered rats. In conclusion, CA prevented oxidative stress, inflammation, and liver injury induced by MTX by activating Nrf2 /HO-1 signaling and PPARγ.