Following cytotoxic nanoconjugates from injection to halting the cell cycle machinery and its therapeutic implications in oral cancer.

BACKGROUND: The concept of personalized therapy has been proven to be a promising approach. A popular technique is to utilize gold nanoparticles (AuNPs) as drug delivery vectors for cytotoxic drugs and small molecule inhibitors to target and eradicate oral cancer cells in vitro and in vivo. Both drug and nanocarrier designs play important roles in the treatment efficacy. In our study, we standardized the nanosystem regarding NPs type, size, surface ligands and coverage percentage leaving only the drugs mode of action as the confounding variable. We propose that similarly constructed nanoparticles (NPs) can selectively leverage different conjugated drugs irrelevant to their original mode of action. If proven, AuNPs may have a secondary role beyond bypassing cancer cell membrane and delivering their loaded drugs. METHODS: We conjugated 5- fluorouracil (5Fu), camptothecin (CPT), and a fibroblast growth factor receptor1-inhibitor (FGFR1i) to gold nanospheres (AuNSs). We followed their trajectories in Syrian hamsters with chemically induced buccal carcinomas. RESULTS: Flow cytometry and cell cycle data shows that 5Fu- and CPT- induced a similar ratio of S-phase cell cycle arrest as nanoconjugates and in their free forms. On the other hand, FGFR1i-AuNSs induced significant sub-G1 cell population compared with its free form. Despite cell cycle dynamics variability, there was no significant difference in tumor cells' proliferation rate between CPT-, 5Fu- and FGFR1i- AuNSs treated groups. In our in vivo model, FGFR1i-AuNSs induced the highest tumor reduction rates followed by 5Fu- AuNSs. CPT-AuNSs induced significantly lower tumor reduction rates compared with the 5Fu- and FGFR1i- AuNSs despite showing similar proliferative rates in tumor cells. CONCLUSIONS: Our data indicates that the cellular biological events do not predict the outcome seen in our in vivo model. Furthermore, our results suggest that AuNSs selectively enhance the therapeutic effect of small molecule inhibitors such as FGFR1i than potent anticancer drugs. Future studies are required to better understand the underlying mechanism.

Urinary Cellular Profile as a Biomarker for Lupus Nephritis.

BACKGROUND/OBJECTIVE: A search for the ideal biomarker for lupus nephritis (LN) is still underway, one that can be used for early detection and correlate with the class and activity of LN. Urine is normally devoid of leukocytes; however, it has been observed that macrophages and T lymphocytes are routinely present in the urine of LN patients and those with other proliferative renal diseases. This provides the idea for their potential use as biomarkers for proliferative LN. Here, we measured the urinary CD4+, CD8+ T lymphocytes, and CD14+ monocytes in patients with systemic lupus erythematosus (SLE) as potential biomarkers for LN. METHODS: A longitudinal case-control study included 30 SLE patients with LN, 30 SLE patients without past or current LN, and 20 healthy subjects as a control group. The flow cytometric analysis was done using BD FACS Calibur multiparameter flow cytometer equipped with BD CellQuest Pro software for data analysis. RESULTS: CD14+ cells were the most abundant cells in the urine of LN patients. The mean numbers of urinary CD8+, CD4+, and CD14+ cells/mL were significantly higher in patients with LN than in those without. The cell counts correlated significantly with proteinuria. Urinary CD14+ cells seem to occur in much higher counts in class IV than class III LN. CONCLUSIONS: Urinary CD8+, CD4+, and CD14+ cells are highly sensitive and specific markers for detecting proliferative LN. A low CD4:CD8 ratio provides a further clue. Urinary CD14 cell counts may be a potential biomarker to differentiate between the different classes of proliferative LN.

Study of serology and genetics of celiac disease in patients with juvenile systemic lupus erythematosus 'celiac in juvenile systemic lupus'.

INTRODUCTION: Several case reports and case series have suggested a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Patients with CD developing SLE and vice versa have been reported, highlighting a possible association. Up to 23% of patients with CD have raised anti-double-stranded DNA and likewise 5-22% of SLE patients are seropositive for CD. OBJECTIVE: Aim was to screen for CD in the serum of patients suffering from juvenile SLE (JSLE). METHODS: One hundred JSLE patients and 40 (age- and sex-matched) healthy subjects were subjected to laboratory screening for CD, endoscopic examination and histopathological examination of the duodenal biopsies to confirm CD diagnosis (in seropositive cases only). RESULTS: tTG Ab tested positive in 10% and negative in 90% of patients. tTG Ab correlated significantly with Systemic Lupus Erythematosus Disease Activity Index score (P < 0.001) and insignificantly with hemoglobin and C-reactive protein. Esophago-gastro-duodenoscopy was done to all 10 patients with positive serology for CD revealing six patients with manifest celiac (positive serology and positive endoscopy/biopsy) and four cases of latent celiac (positive serology and negative endoscopy/biopsy). CONCLUSION: Most CD patients with articular symptoms remain undiagnosed, which makes screening justified in high-risk patients with autoimmune diseases. This study highlights the strong relationship between JSLE and CD and the need to screen JSLE patients and also other auto-immune rheumatic diseases for the concomitant existence of CD.

CD200/CD200 receptor axis in psoriasis vulgaris.

BACKGROUND: Psoriasis is a chronic inflammatory multisystem disease with imbalance between the Th17 and T regulatory sub-populations. CD200/CD200R is an anti-inflammatory/immune-suppressive axis that might contribute to its pathogenesis given its relation to the Tregs induction. The current study aimed to investigate the status of the CD200/CD200R axis in the blood of psoriasis vulgaris patients versus healthy controls. METHODS: In this comparative cross sectional study, the blood levels of sCD200 and CD200R levels were measured in 25 psoriasis vulgaris patients and an age and sex matched 25 healthy controls using ELISA and flow-cytometry respectively. Their levels were tested for correlation to disease severity. RESULTS: sCD200 was significantly higher while CD200R was significantly lower in psoriasis vulgaris patients than in controls. They did not correlate to each other or to psoriasis severity although they differed significantly among cases of different severities. CONCLUSION: Aberrant expression of CD200/CD200R might play a role in psoriasis vulgaris pathophysiology and disease severity. It might constitute a future target of therapy, but cannot be used as a marker of disease severity.

Seminal levels of angiotensin II and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients: Relation to fertility status.

Several theories were proposed to explain the pathophysiology of varicocele-related infertility seen in some patients. Our aim was to study the levels of angiotensin II in semen and angiotensin II type 2 receptor expression on spermatozoa in varicocele patients in relation to their fertility status and to evaluate the influence of varicocelectomy on their levels in infertile varicocele patients. Thirty fertile and 30 infertile varicocele patients and 30 healthy controls were subjected to measurement of reproductive hormones, semen analysis, measurement of seminal angiotensin II and evaluation of angiotensin II type 2 receptor expression on spermatozoa. Infertile varicocele patients underwent varicocelectomy and were re-evaluated for the same parameters after the operation. Sperm concentration, morphology, progressive motility, seminal angiotensin II and angiotensin II type 2 receptor expression were significantly lower in infertile varicocele patients compared with the other groups. Post-operative values showed significant increase in the studied parameters compared with the pre-operative values but not to other two groups. A significant positive correlation between angiotensin II type 2 receptor expression and progressive motility was detected in all studied groups. In conclusion, dysregulation of angiotensin II and angiotensin II type 2 receptor in varicocele patients may be involved in varicocele-related infertility.