The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study.

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK-GABA-CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK-GABA-CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK-GABA-CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK-GABA combination and AMK-GABA-CSNPs on the renal tissue, 42 healthy Sprague-Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK-GABA-CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK-GABA-CSNPs (30 mg/kg/day; i.p.). The results showed that AMK-GABA-CSNPs formulation is superior to unloaded AMK-GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK-GABA-CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

The Contribution of Serum Sialic Acid Binding Immunoglobulin-Like Lectin 1(sSIGLEC-1) as an IFN I Signature Biomarker in the Progression of Atherosclerosis in Egyptian Systemic Lupus Erythematosus (SLE) Patients.

Clinical symptoms of systemic lupus erythematosus (SLE), such as atherosclerosis and related cardiovascular diseases, are caused by inflammatory cytokines and endothelial cell damage. The serum sialic acid binding immunoglobulin-like lectin 1 (sSIGLEC-1) is thought to be an alternative biomarker of IFN signature and may have a role in the pathogenesis of atherosclerosis. The aim of the study was to measure the levels of sSIGLEC-1 in the serum of SLE patients in comparison to a control group and examine the associations between sSIGLEC-1, SLEDAI, lipid profile, oxidized low density lipoprotein (oxLDL), and carotid intima media thickness (CIMT) to investigate whether sSIGLEC-1 participates in the development of atherosclerosis. sSIGLEC-1 levels were tested in 53 patients and 20 volunteers using ELISA kit. Duplex measurements were performed on all subjects to measure CIMT. SLE patients had significantly higher values of sSIGLEC-1 (P < 0.0001), total cholesterol (P = 0.029), triglycerides (P = 0.001), low density lipoprotein (P = 0.032), oxLDL (P = 0.001), right CIMT (P = 0.0099) and a significantly lower value of high-density lipoprotein (P = 0.04) when compared to controls. sSIGLEC-1 had significant positive correlations with right CIMT (r = 0.5, P < 0.0002) and oxLDL (r = 0.67, P < 0.0001) in all SLE patients. When compared to non-dyslipidemic patients, the dyslipidemic group exhibited significantly higher levels of all previous parameters except HDL and left CIMT. Circulating form of SIGLEC-1 accelerates atherosclerosis and provides a simple way to predict the occurrence of atherosclerosis in SLE patients.

Preparation of polyclonal anti-Schistosoma mansoni cysteine protease antibodies for early diagnosis.

In many parts of the tropics, schistosomiasis is a major parasitic disease second only to malaria as a cause of morbidity and mortality. Diagnostic approaches include microscopic sampling of excreta such as the Kato-Katz method, radiography, and serology. Due to their vital role in many stages of the parasitic life cycle, proteases have been under investigation as targets of immunological or chemotherapeutic anti-Schistosoma agents. Five major classes of protease have been identified on the basis of the peptide hydrolysis mechanism: serine, cysteine, aspartic, threonine, and metalloproteases. Proteases of all five catalytic classes have been identified from S. mansoni through proteomic or genetic analysis. The study aimed to produce polyclonal antibodies (pAbs) against schistosomal cysteine proteases (CP) to be used in the diagnosis of schistosomiasis. This study was conducted on S. mansoni-infected patients from highly endemic areas and from outpatients' clinic and hospitals and other patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids). In this study, the produced polyclonal antibodies against S. mansoni cysteine protease antigens were labeled with horseradish peroxidase (HRP) conjugate and used to detect CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA. The study involved 200 S. mansoni-infected patients (diagnosed by finding characteristic eggs in the collected stool samples), 100 patients infected with other parasites (Fasciola, hookworm, hydatid, and trichostrongyloids), and 100 individuals who served as parasite-free healthy negative control. The prepared pAb succeeded in detecting CP antigens in stool and serum samples of S. mansoni-infected patients by sandwich ELISA with a sensitivity of 98.5% and 98.0% respectively. A positive correlation was observed between S. mansoni egg counts and both stool and serum antigen concentrations. Purified 27.5 kDa CP could be introduced as a suitable candidate antigen for early immunodiagnosis using sandwich ELISA for antigen detection. KEY POINTS: • Detection of cysteine protease antigens can replace parasitological examination. • Sandwich ELISA has a higher sensitivity than microscopic examination of eggs. • Identification of antigens is important for the goal of obtaining diagnostic tools.

Eobania vermiculata whole-body muscle extract-loaded chitosan nanoparticles enhanced skin regeneration and decreased pro-inflammatory cytokines in vivo.

BACKGROUND: Usually, wounds recover in four to six weeks. Wounds that take longer time than this to heal are referred to as chronic wounds. Impaired healing can be caused by several circumstances like hypoxia, microbial colonization, deficiency of blood flow, reperfusion damage, abnormal cellular reaction and deficiencies in collagen production. Treatment of wounds can be enhanced through systemic injection of the antibacterial drugs and/or other topical applications of medications. However, there are a number of disadvantages to these techniques, including the limited or insufficient medication penetration into the underlying skin tissue and the development of bacterial resistance with repeated antibiotic treatment. One of the more recent treatment options may involve using nanotherapeutics in combination with naturally occurring biological components, such as snail extracts (SE). In this investigation, chitosan nanoparticles (CS NPs) were loaded with an Eobania vermiculata whole-body muscle extract. The safety of the synthesized NPs was investigated in vitro to determine if these NPs might be utilized to treat full-skin induced wounds in vivo. RESULTS: SEM and TEM images showed uniformly distributed, spherical, smooth prepared CS NPs and snail extract-loaded chitosan nanoparticles (SE-CS NPs) with size ranges of 76-81 and 91-95 nm, respectively. The zeta potential of the synthesized SE-CS NPs was - 24.5 mV, while that of the CS NPs was 25 mV. SE-CS NPs showed a remarkable, in vitro, antioxidant, anti-inflammatory and antimicrobial activities. Successfully, SE-CS NPs (50 mg/kg) reduced the oxidative stress marker (malondialdehyde), reduced inflammation, increased the levels of the antioxidant enzymes (superoxide dismutase and glutathione), and assisted the healing of induced wounds. SE-CS NPs (50 mg/kg) can be recommended to treat induced wounds safely. SE was composed of a collection of several wound healing bioactive components [fatty acids, amino acids, minerals and vitamins) that were loaded on CS NPs. CONCLUSIONS: The nanostructure enabled bioactive SE components to pass through cell membranes and exhibit their antioxidant and anti-inflammatory actions, accelerating the healing process of wounds. Finally, it is advised to treat rats' wounds with SE-CS NPs.

The potential use of serum interleukin-21 as biomarker for lupus nephritis activity compared to cytokines of the tumor necrosis factor (TNF) family.

OBJECTIVE: Lupus nephritis (LN) is a significant consequence of systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first work that focuses on evaluation of serum interleukin (IL-) 21 as a diagnostic biomarker of LN activity, compared to B lymphocyte stimulator (BlyS), tumor necrosis factor ligand superfamily member 13 (TNF-SF13), and traditional techniques of active LN attempting to compare their diagnostic usefulness. METHODS: Serum levels of IL-21, BlyS, and TNF-SF13 during LN were investigated. Twenty-five biopsy-proven, active LN female patients and 15 SLE patients without active LN and 20 healthy controls (HCs) joined this work. RESULTS: Serum IL-21 level was significantly higher in active LN group than in inactive LN group. Correlation analysis showed that serum IL-21 levels were significantly correlated with total SLEDAI (r = 0.41, p = 0.03), renal-SLEDAI (r = 0.48, p = 0.04), renal activity index (AI) (r = 0.93; p < 0.001), and 24-h proteinuria (r = 0.51; p > 0.008). Receiver operating characteristic curve (ROC) revealed the ability of serum IL-21 to discriminate between active and inactive LN with 70% sensitivity at >240 pg/ml cutoff point (AUC 0.809). CONCLUSION: For Egyptian SLE patients, serum levels of IL-21 were superior to TNF-SF13 and BlyS and correlated significantly with the activity indexes of LN, indicating a promising role as a potential biomarker of active LN.

The hidden hazardous effects of stevia and sucralose consumption in male and female albino mice in comparison to sucrose.

Replacing sucrose with non-caloric sweeteners is an approach to avoid overweight and diabetes development. Non-caloric sweeteners are classified into either artificial as sucralose or natural as stevia. Both of them have been approved by FDA, but the effects of their chronic consumption are controversial. The present study aimed to evaluate the effects of these two sweeteners, in male and female albino mice, on different blood biochemical parameters, enzymes activities and immunological parameters after 8 and 16 weeks of sweeteners administration. 40.5 mg/ml of sucrose, 5.2 mg/ml of sucralose and 4.2 mg/ml of stevia were dissolved individually in distilled water. Mice were administrated by sweetener's solution for 5 h daily. Male and female mice showed a preference for water consumption with sucralose or stevia. Both of the two sweeteners significantly reduced the hemoglobin level, HCT%, RBCs and WBCs count. After 18 weeks, significant elevations in liver and kidney function enzymes were observed in male and female mice administrated with both non-caloric sweeteners. Histopathological examination in sucralose and stevia administrated groups confirmed the biochemical results; where it revealed a severe damage in liver and kidney sections. While, sucrose administration elevated, only, the levels of ALT, AST and cholesterol in male mice. A vigorous elevation in levels of different immunoglobulin (IgG, IgE and IgA) and pro-inflammatory cytokines (IL-6 and -8), that was accompanied by a significant reduction in level of anti-inflammatory cytokine IL-10, was observed in male and female mice groups administrated with sucralose or stevia. On the other hand, sucrose administration led to an elevation in IgA and reduction in IL-10 levels.

Impact of cow, buffalo, goat or camel milk consumption on oxidative stress, inflammation and immune response post weaning time.

Milk is a whitish liquid that is secreted from mammary glands; and considered as the primary source of nutrition for newborns since they are not able to digest solid food. However, it contains primary nutrients, as well as growth and immune factors. Early weaning is a critical issue that face women and their babies in developing countries. To avoid infant malnutrition, they tend to use other milk types instead of baby formula. Therefore, the present study aimed to evaluate the impact of cow, buffalo, goat or camel milk consumption on oxidative stress, inflammation and immune response in male and female Sprague Dawley rats post weaning time. The amino acids, fatty acids, minerals and vitamins in the tested milk types were evaluated. Animals were divided into 5 groups (control, cow, buffalo, goat and camel milk administrated groups) (10 rats/group); each animal was administrated by 3.4 ml/day. Rats were administered with milk for 6 weeks; at the end of the 5th week, five animals of each group were isolated and the remaining five animals were immunized with sheep red blood cells (SRBCs) and kept for another week to mount immune response. The effect of different milk types on rats' immune response towards SRBCs was evaluated through pro-inflammatory cytokines, antioxidants, ESR and CRP measurement; together, with the histopathological examination of spleen samples and hemagglutination assay. Camel milk consumption reduced oxidative stress and inflammation in spleen that resulted from SRBCs immunization; in addition to, B cell stimulation that was apparent from the high level of anti-SRBCs antibodies. Camel milk is recommended for newborn consumption, due to its high-water content, unsaturated fatty acids, and vitamin C, as well as low lactose and fat content.

Desert date seed extract-loaded chitosan nanoparticles ameliorate hyperglycemia and insulin deficiency through the reduction in oxidative stress and inflammation.

Plants represents a huge source of bioactive materials that have been used since the old times in the treatment of many diseases. Balanites aegyptiaca, known as desert date, has been used in treatment of fever, diabetes and bacterial infection. Desert dates contains a hard seed that resembles 50-60% of the fruit. The seed extract contains many fatty acids, amino acids and other bioactive materials that gives the extract its antioxidant and anti-inflammatory properties. The study aimed to use Balanites seed extract-loaded chitosan nanoparticles (SeEx-C NPs) for the treatment of streptozotocin (STZ)-induced diabetes in male Sprague Dawley rats. Animals were divided into two main divisions (healthy and diabetic rats). Each division contained seven groups (5 rats/group): control untreated group I, SeEx treated group II and group III (10 and 20 mg/kg b.w., respectively), C NPs treated group IV and group V (10 and 20 mg/kg b.w., respectively) and SeEx-C NPs treated group VI and group VII (10 and 20 mg/kg b.w., respectively). The therapeutical effects of SeEx-C NPs were evaluated through biochemical and immunological assessments in rats' pancreases. The results showed that SeEx-C NPs (10 and 20 mg/kg b.w.) reduced the oxidative stress and inflammation in rats' pancreases allowing the islets neogenesis. The loading of SeEx on C NPs allowed the delivery of fatty acids (oleic, lauric and myristic acid), amino acids (lysine, leucine, phenylalanine and valine) and minerals to pancreatic beta-cells in a sustainable manner. SeEx-C NPs administration successfully increased insulin secretion, allowed pancreatic islets neogenesis and reduced oxidative stress and inflammation.

Preparation of chitosan nanoparticles loaded with Balanites aegyptiaca extract for treatment of streptozotocin-induced diabetes in rats.

Diabetes mellitus is characterized by elevated blood sugar level due to a deficiency in insulin production and/or action. Balanites aegyptiaca (BA) has been employed as a hypoglycemic medication. Nanoparticles (NPs) have many advantages like minimized drug dose, sustainable drug release, maximized bioavailability and delivery of drugs. The study aimed to synthesize novel chitosan (CS) NPs loaded with BA extract (BA Ex). The prepared NPs were examined in treatment of streptozotocin-induced diabetes in rats. The anti-diabetic efficiency was evaluated through measuring of levels of blood glucose, insulin, lipid profile, oxidative stress markers, pro-inflammatory cytokines. GC-MS, HPLC and ICP techniques showed the presence of numerous bioactive components that have an anti-diabetic effectiveness. BA Ex-CS NPs succeeded in treatment of diabetes; where, it increased insulin secretion, lowered both FBG and FTA levels and helped in neogenesis of pancreatic islets beta cells. The regenerative activity of BA Ex-CS NPs is attributed to its high antioxidant and anti-inflammatory properties. This antioxidant activity scavenged the generated free radicles that resulted from STZ administration. CS NPs raised the plant extract efficacy, prevented its degradation, and regulated the release of its components. The delivery of BA Ex bioactive components has been revolutionized by CS NPs.

Indole Compounds in Oncology: Therapeutic Potential and Mechanistic Insights.

Cancer remains a formidable global health challenge, with current treatment modalities such as chemotherapy, radiotherapy, surgery, and targeted therapy often hindered by low efficacy and adverse side effects. The indole scaffold, a prominent heterocyclic structure, has emerged as a promising candidate in the fight against cancer. This review consolidates recent advancements in developing natural and synthetic indolyl analogs, highlighting their antiproliferative activities against various cancer types over the past five years. These analogs are categorized based on their efficacy against common cancer types, supported by biochemical assays demonstrating their antiproliferative properties. In this review, emphasis is placed on elucidating the mechanisms of action of these compounds. Given the limitations of conventional cancer therapies, developing targeted therapeutics with enhanced selectivity and reduced side effects remains a critical focus in oncological research.

Melatonin loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles reduce inflammation, inhibit apoptosis and protect rat's liver from the hazardous effects of CCL4.

Liver is an important organ that carries out major important functions including the detoxification of harmful chemicals. Numerous studies have lately focused on the impact of various substances, such as chemical pollutants and pharmaceutical drugs, on the liver. Melatonin (Mel) has been reported for the protection against liver injury. In order to enhance Mel therapeutic benefits and prevent any potential negative effects, Mel has to be delivered to the injured liver. Therefore, the goal of the current investigation was to create Mel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Mel-PLGA NPs) to alleviate carbon tetrachloride (CCL4)-induced liver damage in male Sprague Dawley rats. The prepared Mel-PLGA NPs were physically characterized to determine its size and charge. Moreover, Mel-PLGA NPs were examined, in vitro, to determine its antioxidant, anticoagulant, anti-inflammatory and cytotoxicity effects before being used in vivo. The effect of NPs on liver injury was evaluated through biochemical, immunological, histopathological examination and flow cytometry technique. Mel-PLGA NPs were smooth and spherical with no signs of aggregation and have in vitro antioxidant, anti-inflammatory and anticoagulant effects. NPs varied in size from 87 to 96 nm in transmission electron microscope images, while their hydrodynamic diameter was 41 nm and their zeta potential was -6 mV. Mel-PLGA NPs had encapsulation efficiency (EE%) and drug loading (DL%) of 59.9 and 12.5%, respectively. Treatment with Mel-PLGA NPs ameliorated all histopathological changes, in liver sections, that resulted from CCL4 administration; where, liver sections of treated groups were similar to those of healthy control GI. NPs administration were superior to free Mel and reversed the elevated levels of liver function enzymes, inflammatory cytokines and matrix metalloproteinases to their normal levels. Moreover, liver sections of groups treated with NPs showed negative immunostaining for nuclear factor-κB (NF-κB) and C-reactive protein indicating their anti-inflammatory behavior. Mel-PLGA NPs significantly protected liver from the toxicity of CCL4. The effective dose of NPs was 5 mg/kg indicating a reduction in the required Mel dose and its associated adverse effects.

Anti-Cryptosporidium oocysts polyclonal antibodies for cryptosporidiosis diagnosis and protection.

Cryptosporidiosis is an intestinal infection that is triggered by the protozoan parasite Cryptosporidium spp. Cryptosporidium oocysts can spread from one host to another either through direct contact with infected hosts' faeces or through indirect means (consumption of contaminated water or food). Significant numbers of oocysts are produced as a result of the rapid growth of the parasite within the infected hosts. For proper care of cryptosporidiosis, a laboratory diagnosis is necessary. Therefore, this study aimed to produce anti-Cryptosporidium parvum (C. parvum) oocyst immunoglobulin (Ig)G polyclonal antibodies (pAbs). The produced pAbs were used in the detection of C. parvum oocysts antigens in stool and serum samples of infected calves. Moreover, pAbs were tested in protection of balb-c male mice from cryptosporidiosis infection. C. parvum oocysts were used in the preparation of antigens to be used in the immunization of New Zealand white rabbits. pAb was purified by ammonium sulphate precipitation method, caprylic acid purification method and diethylaminoethyl (DEAE) anion exchange chromatographic method. Sandwich enzyme-linked immunosorbent assay (ELISA) (using prepared pAb) scored higher sensitivity (85% and 95% for serum and stool samples) than that (80%) of microscopic examination of stool samples. Moreover, pAb significantly reduced the oocysts shedding, decreased inflammatory cytokines and enhanced the loss in the body weight of protected animals. The prepared pAb succeeded in the diagnosis of cryptosporidiosis in calves with high sensitivity either in the serum or stool samples. Our results indicated the usefulness of using the prepared pAb in protection against cryptosporidiosis.

Novel grape seed extract nanoparticles attenuate amikacin-induced nephrotoxicity in rats.

Amikacin (AMK), an antibiotic, is prescribed for treating various bacterial diseases like urinary tract infections, encephalitis, asthma and joint infections. The most significant side effects, which affect 1 to 10% of consumers, are kidney injury and ototoxicity. Several studies discussed the role of grape seed extract (GSE) in renoprotection against AMK. The current study aimed to extract Muscat of Alexandria grape seeds followed by its characterization to determine its bioactive components and elements. GSE nanoparticles was prepared and tested, in vitro, to determine its safety for the in vivo experiment. Experimental groups were control group I, AMK group II, GSE (50 mg/kg)-AMK group III, GSE (100 mg/kg)-AMK group IV, GSE NPs (25 mg/kg)-AMK group V and GSE NPs (50 mg/kg)-AMK group VI. Groups 2-6 received 100 mg/kg/day of AMK by intramuscular injection for two weeks for the induction of experimental nephrotoxicity. Groups 3-6 received daily doses of GSE or GSE NPs by oral gavage, concurrently, with AMK for two weeks. GSE was rich in polyphenol compounds like proanthocyanidins, phenolic acids like gallic and egallic acids, catechine and epicatechine. GSE NPs have a smooth surface and a size that ranged from 40 to 70 nm; and have an anti-oxidant, anti-inflammatory, anti-cytotoxic and anti-microbial in vitro effects. It reduced oxidative stress and inflammation that followed AMK administration; and attenuated the AMK-induced nephrotoxicity. GSE NPs were safe to be used in vivo as a renoprotective agent against AMK; where, it reduced the oxidative stress and inflammation.

Therapeutic effect of melatonin-loaded chitosan/lecithin nanoparticles on hyperglycemia and pancreatic beta cells regeneration in streptozotocin-induced diabetic rats.

Nanotechnology is used to overcome fundamental flaws in today's marketed pharmaceuticals that obstruct therapy, like restricted solubility and quick release of drugs into the bloodstream. In both human and animal researches, melatonin was demonstrated to regulate glucose levels. Despite the fact that melatonin is quickly transported through the mucosa, its sensitivity to be oxidized creates a difficulty in achieving the required dose. Additionally, due to its variable absorption and poor oral bioavailability necessitates the development of alternative delivery methods. The study aimed to synthesize melatonin loaded chitosan/lecithin (Mel-C/L) nanoparticles to be assessed in the treatment of streptozotocin (STZ)-induced diabetes in rats. The antioxidant, anti-inflammatory, and cytotoxicity properties of nanoparticles were estimated to determine the safety of manufactured nanoparticles for in vivo studies. In addition, Mel-C/L nanoparticles were administered to rats for eight weeks after inducing hyperglycemia. The therapeutic effect of Mel-C/L nanoparticles was assessed in all experimental groups by detecting insulin and blood glucose levels; observing improvements in liver and kidney functions as well as histological and immunohistochemical evaluation of rats' pancreatic sections. The results proved that Mel-C/L nanoparticles showed remarkable anti-inflammatory, anti-coagulant, and anti-oxidant effects, in addition to its efficiency in reducing blood glucose levels of STZ-induced diabetic rats and great ability to promote the regeneration of pancreatic beta (ß)-cells. Furthermore, Mel-C/L nanoparticles elevated the insulin level; and decreased the elevated levels of urea, creatinine and cholesterol. In conclusion, nanoparticles application decreased the administrated melatonin dose that in turn can diminish the side effects of free melatonin administration.

Dual role of melatonin as an anti-colitis and anti-extra intestinal alterations against acetic acid-induced colitis model in rats.

The available ulcerative colitis drugs exhibit limited outcomes and adverse side effects. Therefore, our study aimed to investigate the therapeutic efficacy of melatonin in acetic acid (AA)-induced colitis to establish a possible treatment for colitis and its impacts on vital organs. Following colitis induction (2 ml 5% AA, rectally), rats were orally received melatonin (5 mg/kg) once per day for 6 days after colitis induction. Then, histopathological examination of colon, kidney, liver, and spleen was conducted, interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and total antioxidant capacity (TAC) levels were assessed in colon tissue. Colitis induction in untreated rats caused necrotic effects in colon tissues, a significant increase in colonic IL-1ß, TNF-α, MPO, and MDA levels, and a remarkable decrease in GSH and TAC levels in colon tissue in comparison to the control group. Meanwhile, melatonin treatment reversed these parameters by improving the microscopic and macroscopic colitis features and extra-intestinal (kidney, liver, and spleen) changes in all treated rats compared to the colitis control group. These results denote a reduction in colitis severity due to the anti-inflammatory and anti-oxidative effects of melatonin and its positive impact on the vital organs.

Garlic (Allium sativum Linnaeus) improved inflammation and reduced cryptosporidiosis burden in immunocompromised mice.

ETHNOPHARMACOLOGICAL RELEVANCE: For thousands of years, garlic (Allium sativum Linnaeus) has been consumed in food and health by numerous civilizations. Cryptosporidium (C.) parvum is an apicomplexan parasite that causes a gastrointestinal disease, with the most common symptoms being watery diarrhea. Although several substances have been tried for its anti-cryptosporidial action, there is no effective treatment for Cryptosporidium disease, especially in immunocompromised individuals. The present study aimed firstly to characterize the bio-active compounds in Allium sativum L. and secondly to evaluate its efficacy as a therapy for cryptosporidiosis especially in immunocompromised mice. MATERIALS AND METHODS: This was accomplished by evaluating the parasitological and histopathological parameters in the experimentally infected immunocompetent and immunocompromised mice. Also, the cytokine profile during the experimental time was recorded through the measuring of T helper (h)1, Th2 and Th17 cells cytokines. Immunosuppressed mice were given 0.25 µg/g per day of dexamethasone orally, before infection with Cryptosporidium parvum oocysts, for fourteen consecutive days. Starting 10 days post infection (PI), nitazoxanide (100 mg/kg per day) or Allium sativum (50 mg/kg per day) was given orally for fourteen consecutive days. RESULTS: Our results showed that oocyst shedding, on the 32nd day PI, in immunocompromised infected group treated with Allium sativum (354.11, 99.35% PR) showed a significant decrease when compared to its corresponding group treated with nitazoxanide (4369.14, 92.05% PR). On the 32nd day PI, all cytokines levels have been decreased to levels that were similar to those of their uninfected corresponding control groups; also, the histopathological changes and the loss in animals' body weight had been improved. Treatment with nitazoxanide did not result in infection clearance or a reduction in the increased cytokines' levels. CONCLUSION: Allium sativum L. displayed high efficacy as a potential therapeutic agent against Cryptosporidium, which supports its traditional usage in parasite diseases.

Taurine loaded chitosan-pectin nanoparticle shows curative effect against acetic acid-induced colitis in rats.

Owing to the poor outcomes and adverse side effects of existing ulcerative colitis drugs, the study aimed to develop an alternative nano-based treatment approach. The study was designed to characterize the in vitro and in vivo properties of taurine, taurine-loaded chitosan pectin nanoparticles (Tau-CS-PT-NPs) and chitosan pectin nanoparticles (CS-PT-NPs) in the therapy of acetic acid (AA)-induced colitis in rats. CS-PT-NPs and Tau-CS-PT-NPs were prepared by ionic gelation method then in vitro characterized, including transmission electron microscopy (TEM), polydispersity index (PDI), zeta potential, Fourier transform infrared (FTIR) spectroscopy, encapsulation efficiency (EE), and drug release profile. Following colitis induction, rats were orally administrated with free taurine, Tau-CS-PT-NPs, and CS-PT-NPs once per day for six days. The sizes of Tau-CS-PT-NPs and CS-PT-NPs were 74.17 ± 2.88 nm and 42.22 ± 2.41 nm, respectively. EE was about 69.09 ± 1.58%; furthermore, 60% of taurine was released in 4 h in simulated colon content. AA-induced colitis in untreated rats led to necrosis of colon tissues and a significant increase in interleukin-1beta (IL-1ß), Tumor Necrosis Factor-alpha (TNF-α), myeloperoxidase (MPO), and malondialdehyde (MDA) levels associated with a remarkable reduction in glutathione (GSH) level in colon tissue in comparison to control group. Treatment with taurine, Tau-CS-PT-NPs, and CS-PT-NPs partly reversed these effects. The present study demonstrated that the administration of free taurine, CS-PT-NPs, and Tau-CS-PT-NPs exerted beneficial effects in acetic acid-induced colitis by their anti-inflammatory and antioxidant activities. The best therapeutic effect was observed in animals treated with taurine-loaded chitosan pectin nanoparticles.

Co-treatment with grape seed extract and mesenchymal stem cells in vivo regenerated beta cells of islets of Langerhans in pancreas of type I-induced diabetic rats.

BACKGROUND: Nowadays, diabetes mellitus is known as a silent killer because individual is not aware that he has the disease till the development of its complications. Many researchers have studied the use of stem cells in treatment of both types of diabetes. Mesenchymal stem cells (MSCs) hold a lot of potential for regenerative therapy. MSCs migrate and home at the damaged site, where they can aid in the repair of damaged tissues and restoring their function. Oxidative stress and inflammation represent a huge obstacle during MSCs transplantation. Therefore, the present study aimed to evaluate the role of grape seed extract (GSE) administration during MSCs transplantation in streptozotocin (STZ)-induced type I diabetes. Furthermore, testing some of GSE components [procyanidins(P)-B1 and P-C1] in conjunction with MSCs, in vivo, was performed to determine if one of them was more effective in relieving the measured attributes of diabetes more than the whole GSE. METHODS: Firstly, GSE was prepared from the seeds of Muscat of Alexandria grapes and characterized to identify its phytochemical components. Experimental design was composed of control group I, untreated diabetic group II, GSE (300 mg/kg)-treated diabetic group III, MSCs (2 × 106 cells/rat)-treated diabetic group IV and GSE (300 mg/kg)/MSCs (2 × 106 cells/rat)-treated diabetic group V. Type I diabetes was induced in rats by intravenous injection with 65 mg/kg of STZ. Treatment started when fasting blood glucose (FBG) level was more than 200 mg/dl; GSE oral administration started in the same day after MSCs intravenous injection and continued daily for 30 consecutive days. RESULTS: The results showed that GSE/MSCs therapy in type I-induced diabetic rats has dramatically managed homeostasis of glucose and insulin secretion; together with, improvement in levels of inflammatory markers and oxidative stress. CONCLUSION: Co-treatment with GSE and MSCs in vivo regenerates beta cells in type I-induced diabetic rats.

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats.

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (ß) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1ß and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated ß cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1ß and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting ß cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.

B-cell activating factor and A proliferation-inducing ligand in relation to intima-media thickness as biomarkers of premature atherosclerosis in systemic lupus erythematosus patients.

BACKGROUND: The aim of this study was to assess the correlation of the serum B-cell activating factor (BAFF), A proliferation-inducing ligand (APRIL) and interleukin (IL)-21 with carotid intima-media thickness (cIMT) to evaluate their efficacy as non-invasive biomarkers for the risk of premature development of atherosclerosis. METHODS: ELISA test was used to quantify serum BAFF, APRIL and IL-21 in 40 patients with systemic lupus erythematosus (SLE) and 20 healthy controls (HCs). The obtained results were correlated with disease duration, anti-double stranded DNA, complement proteins levels, lipid profile, cIMT and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: Serum BAFF, APRIL and IL-21 were significantly increased in SLE compared to HCs. Positive correlation was recorded between BAFF (r = 0.51) and APRIL (r = 0.52) with the cIMT. IL-21 correlated positively with SLEDAI (r = 0.33) and negatively with BAFF (r = -0.37) and APRIL (r = -0.44). According to the multiple logistic regression analysis, we found that low-density lipoprotein, serum BAFF and APRIL values were independent factors for cIMT in SLE. To discriminate premature atherosclerosis in patients with SLE, BAFF ≥455 pg/ml yielded 88.9% sensitivity with 100% specificity while APRIL ≥600 pg/ml yielded 95% sensitivity with 100% specificity. IL-21 ≥240 pg/ml yielded 66.7% sensitivity and 100% specificity. CONCLUSIONS: Circulating BAFF and APRIL in patients with SLE were correlated to disease activity and cIMT, suggesting that they could be used as a peripheral blood biomarker for the occurrence of premature atherosclerosis in SLE.