Perturbation of oral and gut microbiomes has been implicated in alzheimer's disease (AD) along the oral-gut-brain axis; however, the extent of global community restructuring may differ between niches. The present work constitutes a computational interrogation of 16S rRNA profiles from eight-month-old APP/PS1 and wild-type mice, characterizing oral and gut community structure and predicted functional capacity through PICRUSt-driven, KEGG-anchored pathway inference. Comparative taxonomic interrogation disclosed patterns consistent with ectopic occurrence, whereby classically oral genera (Fusobacterium, Streptococcus) were preferentially enriched within intestinal assemblages and gut-typical genera (Muribaculum, Paramuribaculum) emerged as prominent constituents of the oral microbiota in APP/PS1 mice. These cross-niche enrichment patterns, together with significant oral community separation but non-significant gut beta-diversity separation by ANOSIM, were accompanied by predicted decrements in 85 orally enriched enzymes distributed across 25 KEGG pathways, approximately 40 % of which were associated with the biosynthesis of metabolites with reported neuroprotective properties, including glutathione, acetyl-CoA, succinate, malate, formate, lactate, acetate, and monoterpenoids. Systems-level synthesis of these predictions indicated convergent perturbation of antioxidant defenses, bioenergetic circuitry, and one-carbon metabolism, plausibly reflecting metabolic choke points that may favor cognitive deterioration. Although the oral microbiome showed significant inter-cohort separation, the gut microbiome did not, indicating that gut changes are best viewed as taxon-specific shifts within an otherwise stable community. These observations support a hypothesis-generating framework in which oral dysbiosis, selective gut alterations, and cross-niche enrichment patterns are linked to computationally inferred neuroprotective metabolite insufficiency, highlighting specific taxa, enzymes, and pathways as candidates for biomarker and microbiome-targeted therapeutic development in AD.

Nephrotoxicity is characterized by the adverse effects on kidney function caused by various substances, including hazardous chemicals and drugs. This study aimed to investigate the neuroprotective properties of aqueous, methanolic, and ethanolic extracts of Tamarix dioica leaf against acetaminophen-induced kidney damage and compare their efficacy with metformin, a known neuroprotective agent. Thirty-six albino mice were randomly divided into six groups, including a standard control group, an acetaminophen-toxified group, a positive control group treated with metformin (at a dose of 200 mg/kg body weight), and three experimental groups treated with aqueous, methanolic, and ethanolic T. dioica extracts (at a dose of 400 mg/kg body weight each). The neuroprotective potential of the T. dioica extracts was assessed by evaluating hematological markers, electrolyte levels (Na+, K+, Cl-), antioxidant enzymes (CAT, SOD, MDA), renal function tests (urea and creatinine), and toxicity markers (SGOT and SGPT). Additionally, histopathological analysis was conducted to observe any pathological changes in kidney tissues stained with hematoxylin and eosin. The results demonstrated that the T. dioica leaf extracts effectively restored all the indicators and antioxidant enzyme levels to normal, significantly differing from the elevated levels observed in the acetaminophen control group (p < 0.05). Furthermore, histopathological examination revealed regeneration of glomeruli and renal tubules in the stained tissues. These findings suggest that T. dioica leaf extracts can potentially mitigate acetaminophen-induced nephrotoxicity.

This study investigates the anticancer potential of bromelain, a natural proteolytic enzyme derived from pineapple stems, against two of the most prevalent cancers in Saudi Arabia: MCF-7 breast cancer and HepG-2 liver cancer cells. Cell viability was assessed by MTT assay following treatment with increasing concentrations of bromelain for 24 and 48 h, with Taxol serving as a positive control. The anti-migratory effect was evaluated by wound-healing assays, while apoptosis was quantified using Annexin V/7-AAD staining and flow cytometry. Expression of apoptosis-related genes (BAX and BCL2) was analyzed by real-time PCR. Bromelain significantly reduced cancer cell proliferation and migration in a dose- and time-dependent manner, induced both apoptotic and necrotic cell death, and shifted the BAX/BCL2 ratio toward apoptosis. Collectively, these findings demonstrate that bromelain exerts multi-targeted anticancer effects and highlight its potential as a safe, natural adjunct or alternative to conventional chemotherapy in breast and liver cancers.

IntroductionFor many years, 5-fluorouracil (5-FU) has been utilized as a chemotherapeutic treatment for a variety of malignancies. Unfortunately, 5-FU causes cardiotoxicity, which restricts its clinical use. Nifuroxazide (NFX) is a STAT-3 inhibitor with antioxidant and anti-inflammatory effects.MethodsCardiotoxicity was induced by 5-FU (30 mg/kg) once daily for 5 days. NFX was administered in two doses, 25 and 50 mg.ResultsCompared to 5-FU-control rats, NFX significantly attenuates cardiotoxicity induced by 5-FU, as indicated by decreasing creatine kinase (CK)-MB, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) serum levels. Histopathological examinations confirmed the protective effects of NFX against histological abrasions induced by 5-FU. NFX attenuated the oxidative damage induced by 5-FU mediated by peroxisome proliferator-activated receptor gamma (PPAR-γ) signal activation. Moreover, NFX mitigated 5-FU-induced inflammation by suppressing nucleotide-binding domain, leucine-rich repeat-containing protein 3/signal transducer and activator of transcription 3 (NLRP3/STAT3) signal activation. Notably, these protective effects are dose-dependent. Additionally, NFX mitigated 5-FU-induced apoptosis by downregulating Bax, while upregulating Bcl-2.ConclusionsCollectively, NFX attenuated 5-FU-induced cardiac intoxication by regulating NLRP3/STAT-3, PPAR-γ, and Bax/Bcl-2 signals.

Gastric cancer (GC) remains a major global health concern due to its frequent late-stage diagnosis, persistent chemoresistance, and high metastatic potential, all of which contribute to poor clinical outcomes. TRIM26, an E3 ubiquitin ligase with emerging tumor-suppressive functions, has been implicated in various malignancies; however, its precise role in GC has not been fully elucidated. This study elucidates in ferroptosis and chemoresistance while uncovering stromal-tumor crosstalk mechanisms underlying its suppression. Using public databases and clinical GC specimens and established cell lines (MGC-803, HGC27, MKN45), we observed significant downregulation of TRIM26 expression in tumor tissues compared to adjacent normal counterparts (p < 0.001), which correlated with advanced clinical stage and unfavorable prognosis. Functional assays including CCK-8, wound healing, colony formation, and Transwell migration, demonstrated that TRIM26 knockdown significantly enhanced GC cell proliferation, migration, and invasion, whereas TRIM26 overexpression reversed these malignant phenotypes. Mechanistically, TRIM26 induced ferroptosis via HSF1 ubiquitination and degradation, leading to reduced glutathione (GSH) levels and elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Additionally, we identified cancer-associated fibroblast (CAF)-derived exosomal miR-24-3p as a key upstream regulator that directly targets the 3' untranslated region (3' UTR) of TRIM26, thereby suppressing its expression, as confirmed by luciferase reporter assays. In cisplatin-resistant GC models (MGC803/DDP and AGS/DDP), prolonged cisplatin exposure resulted in a pronounced reduction in TRIM26 expression, corresponding with a 5.6-fold increase in IC50 and a heightened metastatic profile. TRIM26 silencing further potentiated chemoresistance and invasive behavior, which coincided with epithelial-mesenchymal transition (EMT), as evidenced by decreased E-cadherin and increased N-cadherin and Vimentin expression. In contrast, TRIM26 restoration re-sensitized resistant GC cells to cisplatin and mitigated their metastatic capacity. Collectively, these findings reveal TRIM26 as a pivotal suppressor of GC progression, acting through the regulation of ferroptosis and EMT while being modulated by stromal exosomal miR-24-3p Therapeutic strategies aimed at restoring TRIM26 expression or disrupting the miR-24-3p/TRIM26/HSF1 axis may offer promising avenues for overcoming chemoresistance and limiting metastasis in GC.

Despite advancements in cancer therapy, hepatocellular carcinoma (HCC) remains a major health concern due to late-stage diagnosis and poor prognosis. In this study, the expression of Glypican-3 (GPC3), a cell surface protein encoded by the GPC3 gene was analyzed at both Messenger RNA and protein levels. The goal was to advance understandings into the role of GPC3 in HCC progression and design a fusion protein as a potential therapy targeting cancer cells expressing this oncogene. Expression analysis of GPC3 in liver hepatocellular carcinoma (LIHC) was performed using GEPIA 2 and OncoDB servers. The analysis revealed a significantly high expression level of GPC3 in cancerous tissues of HCC, with a p-value of p = 1.07e-37. This finding indicates the potential involvement of GPC3 in HCC development. To construct the chimeric proteins (CPs), rituximab, a linker, and an approved Anti-Ogawa O-antigen monoclonal antibody S-20-4 penetrating peptide were combined using trRosetta. The peptide sequence of the Anti-Ogawa O-antigen monoclonal antibody S-20-4, namely, NHNYPPLSLLTF, SHDWRLMLSHLQ, QHDRLLMLSYLV, HHILPPKALLFG, SHTFPPSWLLVR and YSVKPPLPYLPP was obtained from the Immunet BDB database. The HDock scoring algorithms were employed to assess the degree of connection between the CP and the GPC3 gene expressed in HCC. The analysis showed a strong binding affinity of -258.53 KJ/mol between the CP and GPC3, indicating a favorable interaction. Simulations and toxicity analysis further supported the therapeutic potential of the constructed CP for treating LIHC. These findings highlight the potential of the CP as a targeted therapy against HCC, leveraging the high expression of GPC3 in cancerous tissues.

Background This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions. Objective The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression. Methods High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles. Results Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, Vescimonas was more abundant in WT mice, while Odoribacter, Lacrimispora, Helicobacter, Bacteroides, and Alloprevotella were more prevalent in APP/PS1 mice. Conclusions While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites—acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine—that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.

Cadmium (Cd) is a heavy metal with extremely harmful toxic effects on the brain. Quetiapine (QTP) has unique neuroprotective effects with anti-inflammatory and antioxidant actions. However, its neuroprotective effect against Cd-induced neurotoxicity has not been previously studied. QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg. In our study, QTP dose-dependently attenuated neuronal injury by downregulating p-tau and β-amyloid. QTP potently attenuates histological abrasions induced by Cd. QTP counteracted oxidative injury by decreasing neuronal MDA and increased GSH levels mediated by downregulating Keap1 and upregulating Nrf2 and HO-1. QTP mitigated inflammation by decreasing MPO and NO2 and neuronal cytokines TNF-α and IL-1β and upregulating IL-10 levels mediated by NF-κB downregulation. Additionally, QTP counteracted Cd-induced pyroptosis by downregulating caspase-1, ASC, and NLRP3 protein levels. In conclusion, QTP mitigates neurotoxicity induced by Cd through suppression of inflammation, pyroptosis, and oxidative stress by controlling the NF-κB, Keap1/Nrf2, and pyroptosis signals.

BACKGROUND:The growth arrest and DNA damage-inducible 45 (Gadd45) gene has been implicated in various central nervous system (CNS) functions, both normal and pathological, including aging, memory, and neurodegenerative diseases. In this study, we examined whether Gadd45A deletion triggers pathways associated with neurodegenerative diseases including Alzheimer's disease (AD). METHODS:Utilizing transcriptome data from AD-associated hippocampus samples, we identified Gadd45A as a pivotal regulator of autophagy. Comprehensive analyses, including Gene Ontology enrichment and protein-protein interaction network assessments, highlighted Cdkn1A as a significant downstream target of Gadd45A. Experimental validation confirmed Gadd45A's role in modulating Cdkn1A expression and autophagy levels in hippocampal cells. We also examined the effects of autophagy on hippocampal functions and proinflammatory cytokine secretion. Additionally, a murine model was employed to validate the importance of Gadd45A in neuroinflammation and AD pathology. RESULTS:Our study identified 20 autophagy regulatory factors associated with AD, with Gadd45A emerging as a critical regulator. Experimental findings demonstrated that Gadd45A influences hippocampal cell fate by reducing Cdkn1A expression and suppressing autophagic activity. Comparisons between wild-type (WT) and Gadd45A knockout (Gadd45A-/-) mice revealed that Gadd45A-/- mice exhibited significant cognitive impairments, including deficits in working and spatial memory, increased Tau hyperphosphorylation, and elevated levels of kinases involved in Tau phosphorylation in the hippocampus. Additionally, Gadd45A-/- mice showed significant increases in pro-inflammatory cytokines and decreases autophagy markers in the brain. Neurotrophin levels and dendritic spine length were also reduced in Gadd45A-/- mice, likely contributing to the observed cognitive deficits. CONCLUSIONS:These findings support the direct involvement of the Gadd45A gene in AD pathogenesis, and enhancing the expression of Gadd45A may represent a promising therapeutic strategy for the treatment of AD.

The study aimed to develop and analyze a conjugated zinc Nano particle formulation that would enhance its anti-cirrhosis activity by increasing its bioavailability and release. Standard characterization procedures were used to create and analyze zinc nano particles (ZNPs). Drug release and hepatic cirrhosis model testing were conducted on rats utilizing the enhanced formulation. For 30 days, ZnNPs were supplied through oral gavage. For biochemical examination of serum samples, rats were anesthetized and slaughtered after the research. The expression of genes and microRNAs (miRNAs) in liver tissues was studied; together with expression of liver specific genes and inflammatory markers. These findings were also validated by liver tissue histological and immune histochemical (IHC) studies. Measuring techniques demonstrated the practical synthesis and conjugation of ZnNPs. Nanohybrid ZnNPs showed significant anticirrhosis therapeutic activity. ZnNPs' anti-cirrhosis properties decrease TGFR1 and COL3A1 expression, because they enhance the production of miRNAs that protect against cirrhosis. Furthermore, the expression of cancer markers (AFP, p53) was down/up-regulated in ZnNPs treated groups. Similarly, the pro- and anti-inflammatory markers expressions were found normalized in ZnNPs groups compared to untreated groups. These results were further validated by histopathology and IHC analysis, which showed that ZnNPs have anti-fibrotic properties. We finally, conclude that the that we achieve loading capacity of 94%, 36.63%, respectively, in the successful synthesis of ZnNPs. Furthermore, ZnNPs exhibits in vivo hepato-protective activity by down-regulating hepatic cancer markers and upregulating hepatic functional markers which assure the use of ZnNPs for the treatment of liver cirrhosis in future studies.

Several microRNAs (miRNAs) are known to participate in adipogenesis. However, their role in this process, especially in the differentiation of bovine preadipocytes, remains to be elucidated. This study was intended to clarify the effect of microRNA-33a (miR-33a) on the differentiation of bovine preadipocytes by cell culture, real-time fluorescent quantitative PCR (qPCR), Oil Red staining, BODIPY staining, and Western blotting. The results indicate that overexpression of miR-33a significantly inhibited lipid droplet accumulation and decreased the mRNA and protein expression of adipocyte differentiation marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), and fatty acid-binding protein 4 (FABP4). In contrast, the interference expression of miR-33a promoted lipid droplet accumulation and increased the expression of marker genes. Additionally, miR-33a directly targeted insulin receptor substrate 2 (IRS2) and regulated the phosphorylation level of serine/threonine kinase (Akt). Furthermore, miR-33a inhibition could rescue defects in the differentiation of bovine preadipocytes and the Akt phosphorylation level caused by small interfering IRS2 (si-IRS2). Collectively, these results indicate that miR-33a could inhibit the differentiation of bovine preadipocytes, possibly through the IRS2–Akt pathway. These findings might help develop practical means to improve the quality of beef.

The current study aimed to evaluate the efficacy of simultaneous administration of Zingiber officinale (ginger) and Cinnamomum cassia (cinnamon) extracts in mitigating testicular changes associated with diabetes mellitus in rats and to investigate its molecular mode of action. After induction of diabetes using streptozotocin, 36 male rats were divided to six groups namely control, diabetic, metformin-treated, cinnamontreated, ginger-treated and combined, each group having 6 rats. Fasting blood glucose, serum insulin, testosterone was measured. Expression of inflammatory mediators; tumor necrosis factor-alpha (TNF-alpha), Nuclear factor kappa B (NF-kappa B) and Sirtuin 1 (SIRT1) was assessed in the testicular tissue. Histopathological changes in the testis were observed and spermatogenesis and apoptosis were assessed immunohistochemically. The histological and biochemical studies of the untreated group confirmed structural changes in testes induced by diabetes. Oral administration of ginger and cinnamon increased insulin level significantly increased while the blood glucose level significantly decreased in diabetic rats, improving structural testicular changes considerably. Joint intake of ginger and cinnamon increased antihyperglycemic, antioxidant and anti-inflammatory effects markedly improving the testicular injury compared to the administration of either of them. SIRT1 expression in the testis significantly increased in ginger plus cinnamon-treated rats. These results indicate that when administrated together, ginger and cinnamon synergistically enhanced antioxidant, antiapoptotic and anti-inflammatory effects and induced antihyperglycemic effect comparable to metformin. The combination of ginger and cinnamon also upregulated SIRT1 in the testis .

OBJECTIVES:Methotrexate (MTX) is an antimetabolite agent widely used to manage a variety of tumors and autoimmune diseases. Nonetheless, MTX-induced intestinal intoxication is a serious adverse effect limiting its clinical utility. Inflammation and oxidative stress are possible mechanisms for MTX-induced intestinal toxicity. Vinpocetine (VNP) is a derivative of the alkaloid vincamine with potent anti-inflammatory and antioxidant effects. The current study investigated the protective intestinal impact of VNP in attenuating MTX-induced intestinal intoxication in rats. MATERIALS AND METHODS:VNP was administered orally in a dose of 20 mg/kg, while MTX was injected intraperitoneal in a dose of 20 mg/kg. RESULTS:VNP administration attenuated drastic histological changes induced by MTX and preserved both normal villus and crypt histology. VNP significantly attenuated oxidative injury by upregulating intestinal Nrf2 and HO-1 expression. VNP attenuated inflammation by reducing MPO, NO2-, TNF-α, and IL-1β levels mediated by downregulating NF-κB, NDAPH-oxidase, IRF3, p-JAK-1, and p-STAT-3 expressions. Moreover, VNP potently counteracted intestinal necroptosis by effectively downregulating RIPK1, RIPK3, MLKL, and caspase-8 proteins. CONCLUSION:Therefore, VNP may represent a promising approach that can attenuate intestinal toxicity in patients receiving MTX.

Metagenomic approach was used to detect microbial gene abundance and relative abundance in the rhizosphere of Moringa oleifera and surrounding bulk soil and to detect the response of soil microbes to watering. Expectedly, the number and abundance of non-redundant genes were extremely higher in bacteria followed by archaea, eukaryota and viruses. Results demonstrated unexpected high abundance of some microbes (ex., endophyte genus Nocardioides) in the rhizosphere that are supposed to exist mainly in other rhizocompartments. We suggest this differential distribution of microbes is due to the specific pattern of host-microbe interaction. Other endosymbiont microbes, ex., fungi Mucoromycota and Ascomycota, were highly abundant in the bulk soil possibly because they are phytopathogens where plant exudates might inhibit their growth or force these fungi to approach reverse chemotaxis. Our data indicated high abundance of other symbiont microbes in the rhizosphere of M. oleifera at phylum (ex., Actinobacteria) and genus (ex., Streptomyces) levels. Watering experiment indicated that phylum Actinobacteria and the descending genus Streptomyces are among the highest. Rhizobiome of M. oleifera seems to harbor a wealth of new species of the genus Streptomyces that are required to be deciphered for function in order to be eventually utilized in pharmaceutical and agricultural applications.

Cadmium (Cd) is one of the most abundant toxic heavy metals, and its exposure is linked to serious kidney intoxication, a major health problem. Evidence reported that inflammatory damage is a key factor in Cd renal intoxication. Perindopril (PER) is an angiotensin-converting enzyme inhibitor approved for treating hypertension and other cardiovascular problems. Significantly, RAS activation results in inflammatory damage. Our study aimed to examine the renoprotective effects of PER in Cd-induced nephrotoxicity, the impact of inflammation, and the underlying molecular mechanisms. PER was given at a dose of 1 mg/kg per day. Cd was injected at a dose of 1.2 mg/kg, as a single dose. Treatment with PER led to a significant decrease in serum levels of urea, creatinine, uric acid, and urine albumin/creatinine ratio. PER effectively mitigated inflammation by decreasing MPO, NO, IL-1β, IL-6, and INF-γ levels mediated by downregulating NF-κB expression and suppressing JAK-1 and STAT3 phosphorylation. PER modulates Ang II/Ang 1-7 axis in Cd-intoxicated rats by decreasing Ang II expression and increasing Ang-(1-7) expression. PER inhibits Cd-induced apoptosis by lowering Bax, cytochrome c, and cleaved caspase 3 expressions while increasing Bcl-2 expression. In conclusion, PER dampens Cd-induced kidney intoxication by modulating Ang II/Ang 1-7 axis, suppressing NF-κB, JAK-1/STAT3, and apoptosis signals.

Background: Cancer of breast is one of the most popular causes of cancer- related mortality in women. It is a famous condition between women in Saudi arabia, with 21.8% incidence It is rated the second women cancer and its rate is expected to increaseto increase over the next few years. Aim of the Work: focusing on increase the bioavailability of Chia seeds (Chs) and increase its efficiency against breast cancer using nano delivery system. Materials and Methods: Preparation of Chia seeds PLGA-PEG nanoparticles and characterize with Transmission Electron Microscope (TEM), Entrapment efficiency measurement and Particle size distribution with zeta potential analyses. Assessing the anti-breast cancer activity using MTT assay and flow cytometry in addition, the Chs nanoparticles against cell migration using wound healing assay. Results: The TEM image shows spherical NPs with a nano-capsule of PLGA and PEG with Z-average diameters was 62.6 nm. The polydispersity index (PDI) was 0.1 which reflects the high stability of the NPs. Negative charge (zeta potential) showed a consistent pattern on the surface of Chs-loaded PLGA-PEG NPs (ZP= -11.9 mV). Chs NPs exert high cytotoxic effect than Chs. Moreover, the Chs NPs inhibit the cell migration in MCF7 cells. More interestingly that Chs exert apoptosis in breast cancer cells comparing with normal skin fibroblast cells. Conclusion: The present pilot study showed that Chs NPs has anti-Cancer activity and highlight its role as complementary therapy.

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now. Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger ( Zingiber officinale Roscoe) and cinnamon ( Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect. Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague–Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA–β cells were performed. Pancreatic gene expression of β-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques. Results: BGL significantly decreased ( p = 0.01), while serum insulin and TAC significantly increased ( p < 0.001) in both metformin- and ginger plus cinnamon–treated groups compared to the untreated diabetic group. HOMA–β cell index significantly increased ( p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated ( p < 0.001), while β-catenin was insignificantly downregulated ( p = 0.32) in ginger plus cinnamon–treated groups. Insulin immunoexpression in β cells significantly increased ( p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon–treated groups, respectively. Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.

Background: Chemotherapy remains to be the method of choice used by clinicians to treat acute myeloid leukemia (AML) patients. However, the most common problem usually faced in the course of treatment is multidrug resistance (MDR). Nowadays, combination therapy involving natural products as adjuvant therapy to chemotherapy and radiotherapy has been used for many of health problems. Coumarin is a natural compound with known chemotherapeutic activity, as well as other pharmacological properties. We focused on the combination of coumarin and doxorubicin in overcoming of drug-resistance in acute myeloid leukemia. Methods: Cell viability, Apoptotic and necrotic cell death with FACS, oxidative stress detection, and protein expression analysis were used in this study. Results: Coumarin as a single drug exerts a significant cell death on Human acute myeloid leukemia (HL60); however, it does not show the same effect on drug-resistant acute myeloid leukemia (HL60/ADR). Comparing the effects of doxorubicin and coumarin as single drugs versus a combination of coumarin and doxorubicin showed a significant apoptotic cell death. Conclusion: In AML patients, the development of multiple drug resistance (MDR) is the biggest challenge in treating AML patients. Combination therapy with coumarin may be a good choice to overcome the drug resistance in AML patients.

Background: Hepatocellular carcinoma (HCC) is one of the most serious cancers worldwide. Even with recent developments, there has been slight progress in improving the survival of HCC patients. Current therapies are accompanied by huge side effects beside incomplete recovery. Therapy by Herbal shows a marked beneficial effect. Aim: Our study screening of the cytotoxic effect of R. stricta nanoparticles which locally known as “Harmal” against highly aggressive cancer cells (in vitro). Procedures: R. Stricta Nano particles was gained by undergoing R. Stricta sheets to ball milling process to convert particles into Nano scale diameter. Cytotoxicity of different concentrations of nano- Harmal (0.0, 100 and 500 µg/ml) effects on the mRNA expression of Bax and Bcl-2 apoptosis related genes in Hep G-2 and Huh-7cell lines were investigated using real-time quantitative PCR analysis. and MTT assay and FACS analysis Results: It is clear from SEM images that the Harmal nanoparticles are predominantly spherical in shape and polydispersity with particle size around 100 nm. Screening of of Harmal nanoparticles (HNP) after 24 and 48 hours showed a significant cytotoxic effect on all cell lines at 500 μg/ml (p < 0.05) but has a high significant decrease in Hep G-2 cell viability with 100 and 500 μg/ml of HNP Hr(p < 0.001) of treatment compared with other cell lines. Conclusion and clinical relevance: Moving on gene expression and MTT assay and FACS analysis, we concluded that the HNP produced a clear cell death apoptosis in Hep G-2 and Huh-7 cell lines

Two imported thylakoid membrane proteins, PSII-X and PSII-W, are synthesised with cleavable N-terminal signal peptides that closely resemble those of Sec-dependent lumenal proteins. In this report we have reconstituted the insertion of pre-PSII-X and pre-PSII-W into isolated thylakoids. We show that insertion does not require either nucleoside triphosphates or stromal extracts, both of which are required for Sec- and signal recognition particle (SRP)-dependent targeting mechanisms. Insertion is furthermore unaffected by protease treatments that destroy the known protein translocation apparatus in the thylakoid membrane. We conclude that these membrane proteins are inserted by an unusual Sec/SRP-independent mechanism that probably resembles that used by CFoII, and we discuss possible parallels with the biogenesis of phage M13 procoat.