Correlation Between Cyclin D1 Expression With Different Pathological Changes in Colorectum Patients

Background: Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer. Objectives:This study was aimed to detect cyclin D1 in colorectal cancer patients and to correlate cyclin D1 expression with different pathological changes in colorectum.Methods: Tissues microarray paraffin block with 48 colorectal cancer samples were retrieved from the archives of Elrahma Medical Center. The cyclin D1 was analyzed.Results:Cyclin D1 did not correlate with pathological alterations and with tumor grade.Conclusion:Results indicated that; cyclin D1 not correlates with pathological alteration of colorectal cancer.

Liver Histological Abnormalities Were Better Reflected by Virus Level in Chronic Hbv Infected Patients Aged ≤ 30 Years, Hbeag-Positive and Persistently Normal Alt

Background: We analyzed correlations between significant liver histological characteristics and clinical variables in HBV-infected patients and provided recommendations on treatment decisions for patients age younger than 30-year-old.Methods: Liver biopsy was performed on 161 chronic HBV-infected patients with ALT ≤ 40 U/L from July, 2000 – November, 2019. Median age was 39(18-70) years old. Histologic assessment was based on the Scheuer scoring system. Results: Significant necroinflammation and fibrosis were observed in 65.2% (105/161) and 52.2% (84/161) patients of all cases. The pathological abnormality was significantly negatively correlated with viral level in HBeAg-positive subjects, and based on ROC curve analysis, the viral level to predict obvious liver pathological changes was 6.7 log10 IU/ml in those patients. Threshold value of ALT (25 U/L) based on the distribution of ALT and virus levels. Patients younger than 30 years old, almost all had significant pathological alteration with HBV-DNA < 6.7 log10 IU/ml; However, the ratio of insignificant liver’s inflammation and fibrosis were 65% and 70% with HBV-DNA levels ≥ 6.7 log10 IU/ml respectively, on that basis, it could have a further rising, reaching 67.5% and 75% combining with ALT ≤ 25 U/L. Conclusion: Viral load was a better factor to reflect hepatic histological abnormality in Chronic HBV-infected patients with HBeAg-positive and persistently normal ALT whose age ≤ 30 years, 5000000 IU/ml was a suitable threshold.

Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis

Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.

Formulation and Toxicity Evaluation of Nanostructured Lipid Carriers for the Treatment of Acne

Background: Acne vulgarise is an inflammatory disease involving the pathological alteration of the sebaceous glands of the body. It is not a life-threatening disease but has a great influence on lifestyle. Topical combination therapy of vitamin A and antibacterial drugs is an effective treatment for acne. Materials and Methods: The current work investigates the nanostructure lipid colloidal carrier system of Tretinoin and Clindamycin phosphate. Nanostructured lipid carriers (NLCs) were prepared by highspeed homogenization-sonication technique and characterized for physicochemical properties, permeation, in vivo anti-acne and toxicity (acute 2000 mg/Kg, repeat 1000 mg/kg) in Wistar rats. Results: The prepared system was found to be stable, homogenous with more site retention of drugs having non-irritation and toxicity potential. The formulation showed a size of 283 nm, polydispersity index (PDI) 0.43 and Zeta potential (ZP) -37.9 mV with drug entrapment 92.0% and 66.15% for tretinoin and clindamycin respectively. Observed permeation was 18 % and 45% for Tretinoin and Clindamycin less than marketed formulation which is more focused on dermal retention of drug. No significant abnormalities and toxicological symptoms were observed for acute and repeat dose toxicity study for histopathology and haematological examinations of organs. Conclusion: Prepared NLC formulation was aimed at epidermal targeting. Based on obtained results it is concluded that developed lipid-based nanocarrier system of selected drugs showed the targeting potential for effective acne treatment.

Antibiotics Treatment Modulates Microglia–Synapses Interaction

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain function and behavior. Moreover, gut microbiota composition constantly controls microglia maturation, as revealed by morphological observations and gene expression analysis. However, it is unclear whether microglia functional properties and crosstalk with neurons, known to shape and modulate synaptic development and function, are influenced by the gut microbiota. Here, we investigated how antibiotic-mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. Antibiotics treatment was unable to modulate synaptic function in CX3CR1-deficient mice, pointing to an involvement of microglia–neuron crosstalk through the CX3CL1/CX3CR1 axis in the effect of dysbiosis on neuronal functions. Together, our findings show that antibiotic alteration of gut microbiota impairs synaptic efficacy, suggesting that CX3CL1/CX3CR1 signaling supporting microglia is a major player in in the gut–brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

Notch3 Mutation Detection in Stroke Patients and Selective Nanoliposome in Stroke Alleviation in a Mouse Model

This study analyzed the correlation between the Notch3 mutation and stroke by testing an effective nanoparticle-loaded aspirin in stroke therapy. Fifty patients with ischemic stroke were followed for two years, and fifty healthy persons served as the control group. By RT-PCR, this study revealed that the Notch3 mutation existed in ischemic stroke patients who were more likely to have a family history, small vessel lesions, relatively frequent cerebral hemorrhage, and poor long-term prognosis. Liposome-aspirin-chitosan nanoparticle (LACN) was constructed as a nano-composite for stroke treatment. Notch3 Arg170Cys knock-in mice were prepared as a mutant Notch3 mouse model to test the LACN infiltration efficiency and observe the anti-stroke capacity. We found that LACN could better transport aspirin into brain vessels than the Polyethyleneimine (PEI) delivery system. However, in the Notch3 mutation mouse model, cerebral infarction and hemorrhage often occurred after being treated with aspirin. Still, LACN better prolongs the half-life of aspirin, rescues the pathological alteration of stroke in the brain, and reduces inflammatory reaction and oxidative stress response. In conclusion, the Notch3 mutation is closely related to stroke occurrence, and LACN may be a better choice for stroke therapy in the future.

FM-CATH, A Novel Cathelicidin From Fejervarya Multistriata, Shows Therapeutic Potential for Treatment of CLP-Induced Sepsis

Sepsis is an exacerbated inflammatory reaction induced by severe infection. As important defensive molecules in innate immunity, several AMPs are reported to prevent septic shock. In this study, we characterized a novel cathelicidin, FM-CATH, from the frog skin of F. multistriata. FM-CATH was found to adopt an amphipathic α-helix structural in membrane-mimetic environments and possess favorable antimicrobial effects against bacteria and fungus. In addition, it triggered the agglutination of bacteria. It could also strongly bind to LPS and LTA. Additionally, FM-CATH affected the enzymatic activities of thrombin, plasmin, β-tryptase, and tPA, leading to coagulation inhibition in vitro and in vivo. Finally, we observed that FM-CATH improved survival rate and inhibited pathological alteration, bacterial count, serum biochemistry, and pro-inflammatory cytokine expression in the cecal ligation and puncture-induced sepsis mice. Taken together, these findings suggest that FM-CATH might be served as a promising agent for the treatment of sepsis.

Antibiotics Treatment Modulates Microglia-Synapses Interaction Through CX3CL1/CX3CR1 Axis

&lsquo;Dysbiosis&rsquo; of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain func-tion and behavior. Moreover, gut microbiota composition constantly controls microglia matura-tion as revealed by morphological observations and gene expression analysis. However, it is un-clear whether gut microbiota influences microglia functional properties and crosstalk with neu-rons, known to shape and modulate synaptic development and function. Here, we investigated how antibiotic mediated alteration of the gut microbiota influences microglial and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. The effect of dysbiosis on neuronal functions are mediated by microglia-neuron cross-talk through the CX3CL1-CX3CR1 axis, as antibiotics treatment of CX3CR1 deficient mice, mod-ulates microglia density and processes rearrangement leaving unaltered synaptic function. To-gether, our findings show that the antibiotics alteration of gut microbiota impairs synaptic effi-cacy, probably through CX3CL1-CX3CR1 signaling supporting microglia as a major player in in the gut-brain axis, and in particular in the gut microbiota-to-neuron communication pathway.