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1.  Antibody Microarray Analysis of Signaling Networks Regulated by Cxcl13 and Cxcr5 in Prostate Cancer 
Advanced prostate cancer (PCa) often spreads to distant organs, leading to increased morbidity and mortality. It is now well established that chemokines and their cognate receptors play a crucial role in the multi-step process of metastasis. We have previously identified CXCR5 to be highly expressed by PCa tissues and cell lines and its specific ligand, CXCL13, is significantly elevated in the serum of patients with PCa and differentiated PCa cases with other benign prostatic diseases. CXCR5:CXCL13 interactions promote PCa cell invasion, migration, and differential matrix metalloproteinase (MMP) expression. Thus, it is important to understand the molecular and cellular processes that mediate these events. In this study, we quantified changes in apoptosis, cell cycle, and cytoskeleton rearrangement biological pathways from CXCL13-treated hormone refractory PCa cell line (PC3) to better elucidate the signaling pathways activated by CXCL13:CXCR5 interaction. Using antibody arrays that displayed 343 different protein- and phosphorylation-specific antibodies, regulatory networks that control cancer progression signaling cascades were identified. Three regulatory networks were dramatically induced by CXCL13: Akt1/2-cyclin-dependent kinases (Cdk1/2)-Cdk inhibitor 1B (CDKN1B), Integrinβ3-focal adhesion kinase (Fak)/Src-Paxillin(PXN), and Akt-Jun-cAMP response-element binding protein (CREB1). In general, phosphoinositide-3 kinase (PI3K)/Akt and stress-activated protein kinase (SAPK)/c-jun kinase (JNK) were the major signaling pathways modulated by CXCL13 in PCa cells. This cluster analysis revealed proteins whose activation patterns can be attributed to CXCL13:CXCR5 interaction in the androgen-independent PC3 cell line. Taken together, these results suggest that CXCL13 contributes to cell-signaling cascades that regulate advanced PCa cell invasion, growth, and/or survival.
doi:10.4172/jpb.1000232
PMCID: PMC3760521  PMID: 24009409
Akt; Cdk; CDKN1B; Integrin-β3; Fak; Src; Paxillin
2.  Blood gas analysis for bedside diagnosis 
Arterial blood gas is an important routine investigation to monitor the acid-base balance of patients, effectiveness of gas exchange, and the state of their voluntary respiratory control. Majority of the oral and maxillofacial surgeons find it difficult to interpret and clinically correlate the arterial blood gas report in their everyday practice. This has led to underutilization of this simple tool. The present article aims to simplify arterial blood gas analysis for a rapid and easy bedside interpretation. In context of oral and maxillofacial surgery, arterial blood gas analysis plays a vital role in the monitoring of postoperative patients, patients receiving oxygen therapy, those on intensive support, or with maxillofacial trauma with significant blood loss, sepsis, and comorbid conditions like diabetes, kidney disorders, Cardiovascular system (CVS) conditions, and so on. The value of this analysis is limited by the understanding of the basic physiology and ability of the surgeon to interpret the report. Using a systematic and logical approach by using these steps would make the interpretation simple and easy to use for oral and maxillofacial surgeons.
doi:10.4103/0975-5950.127641
PMCID: PMC3961885  PMID: 24665166
Acidosis; alkalosis; blood gas analysis
3.  Differential G protein subunit expression by prostate cancer cells and their interaction with CXCR5 
Molecular Cancer  2013;12:64.
Background
Prostate cancer (PCa) cell lines and tissues differentially express CXCR5, which positively correlate with PCa progression, and mediate PCa cell migration and invasion following interaction with CXCL13. However, the differential expression of G protein α, β, and γ subunits by PCa cell lines and the precise combination of these proteins with CXCR5 has not been elucidated.
Methods
We examined differences in G protein expression of normal prostate (RWPE-1) and PCa cell lines (LNCaP, C4-2B, and PC3) by western blot analysis. Further, we immunoprecipitated CXCR5 with different G protein subunits, and CXCR4, following CXCL13 stimulation. To investigate constitutive coupling of CXCR5 with CXCR4 and PAR-1 we performed invasion assay in PCa cells transfected with Gαq/i2 or Gα13 siRNA, following CXCL13 treatment. We also investigated Rac and RhoA activity by G-LISA activation assay in PCa cells following CXCL13/thrombin stimulation.
Result
Of the 22 G proteins studied, Gαi1-3, Gβ1-4, Gγ5, Gγ7, and Gγ10 were expressed by both normal and PCa cell lines. Gαs was moderately expressed in C4-2B and PC3 cell lines, Gαq/11 was only present in RWPE-1 and LNCaP cell lines, while Gα12 and Gα13 were expressed in C4-2B and PC3 cell lines. Gγ9 was expressed only in PCa cell lines. Gα16, Gβ5, Gγ1-4, and Gγ13 were not detected in any of the cell lines studied. Surprisingly, CXCR4 co-immunoprecipitated with CXCR5 in PCa cell lines irrespective of CXCL13 treatment. We also identified specific G protein isoforms coupled to CXCR5 in its resting and active states. Gαq/11/Gβ3/Gγ9 in LNCaP and Gαi2/Gβ3/Gγ9 in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. Interestingly, Gα13 co-immunoprecipitated with CXCR5 in CXCL13-treated, but not in untreated PCa cell lines. Inhibition of Gαq/i2 significantly decreased the ability of cells to invade, whereas silencing Gα13 did not affect CXCL13-dependent cell invasion. Finally, CXCL13 treatment significantly increased Rac activity in Gαq/i2 dependent manner, but not RhoA activity, in PCa cell lines.
Conclusions
These findings offer insight into molecular mechanisms of PCa progression and can help to design some therapeutic strategies involving CXCR5 and/or CXCL13 blockade and specific G protein inhibition to abrogate PCa metastasis.
doi:10.1186/1476-4598-12-64
PMCID: PMC3720210  PMID: 23773523
Prostate cancer; Chemokine; G proteins; G protein-coupled receptor
4.  Supplemental oxygen therapy: Important considerations in oral and maxillofacial surgery 
The administration of supplemental oxygen is an essential element of appropriate management for a wide range of clinical conditions; crossing different medical and surgical specialities. The present review summarizes the role of supportive oxygen therapy in various clinical conditions encountered in our day-to-day practice in the speciality of oral and maxillofacial surgery; including major trauma, shock, sepsis; perioperative and postoperative considerations and in patients with various other medical comorbidities. Regular and judicious use of oxygen as a drug is thus recommended in our day-to-day practice in oral and maxillofacial surgery to reduce the morbidity and improve the prognosis of patients.
doi:10.4103/0975-5950.85846
PMCID: PMC3304228  PMID: 22442602
Hypoxia; oral surgery; oxygen therapy
5.  Maternal Footprints of Southeast Asians in North India 
Human heredity  2008;66(1):1-9.
We have analyzed 7137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNALys region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.8% and 0.5%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9bp-deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal.
doi:10.1159/000114160
PMCID: PMC2588665  PMID: 18223312
South Asia; 9bp indel; mtDNA; Haplogroup
6.  Maternal Footprints of Southeast Asians in North India 
Human Heredity  2008;66(1):1-9.
We have analyzed 7,137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNALys region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.9 and 0.6%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9-bp deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal.
doi:10.1159/000114160
PMCID: PMC2588665  PMID: 18223312
South Asia; 9bp indel; mtDNA; Haplogroup

Results 1-6 (6)