Bioscience Reports

ObjectivesBone morphogenetic protein-8B (BMP8B) is an adipokine that is synthesized in many tissues and has been shown to be associated with the development of obesity and metabolic disorders in animals and humans. The aim of this study is to investigate the relationship between serum BMP8B levels and various metabolic parameters in women with PCOS. Material and methodsThis cross-sectional study included 80 women with PCOS and 40 age- and BMI-matched controls without PCOS. BMP8B, total cholesterol, triglyceride,fasting blood glucose (FBG), insulin, total testosterone (T),follicle stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2) levels were measured in all the participants. HOMA-IR was used to calculate the insulin resistance. ResultsSerum BMP8B levels were lower in women with PCOS than in healthy women(43.11{+/-}13.09 [ng/mL]vs. 106.45{+/-}52.32 [ng/mL], p< 0.001). HOMA-IR, LH/FSH, total-testosterone, total cholesterol, and triglyceride levels were significantly higher in women with PCOS than controls. Circulating BMP8B levels were positively correlated with HOMA-IR,BMI in PCOS group; was positively correlated with triglyceride in Control group. ConclusionThe low concentration of circulating BMP8B in PCOS may be associated with insulin resistance,Lipid metabolism and BMI,bat may be a new target for PCOS treatment.

Type 2 Diabetes Mellitus (T2DM) is caused by pancreatic beta cell failure and alpha cell dysfunction that are central to this disease pathophysiology. For T2DM, the Peptidylglycine Alpha-Amidating Monooxygenase (PAM) gene has susceptible locus as identified by Genome-wide association studies (GWAS) though underlying molecular mechanisms remained poorly characterised. This study have explored comprehensive in-silico characterization of the PAM gene potential role in T2DM. InterPro was employed to identify protein family and it was observed it belongs to Peptidylglycine alpha-hydroxylating monooxygenase/peptidyl-hydroxyglycine alpha-amidating lyase family (IR000720), consisting of two catalytic domains and nine active regions. Clinically significant 153 genetic variants including non-synonymous SNPs within the locus were identified after analysis of dbSNP through UCSC Genome Browser. Intrinsically disrupted large region (aa 290-495) was observed during protein disorder prediction by utilizing IUPred-3. Ensembl and NCBI BLAST were used to analyse evolutionary conservation sites. This analysis resulted in high sequence similarity with common model organisms Mus musculus and Rattus norvegicus with similarity 90% and 89% respectively. These computational findings suggest specific PAM variants likely to disrupt protein function, providing validated future direction for experimental studies to confirm PAM gene pivotal role in T2DM.

F-box motif encoding YDR131C is functionally uncharacterized gene which forms the complex with the SCF-E3 ligase. The F-box motif containing proteins are involved in substrate recruitment for the ubiquitination and subsequent degradation through 26S proteasome. Autophagy gene, ATG1 (ULK1in human) is a well conserved serine-threonine kinase, required for vesicle formation and cytoplasm to vacuole targeting pathway. Atg1p forms the complex with Atg13p and Atg17p during autophagy. The understanding of crosstalk between ubiquitin and autophagy pathways is crucial for synthetic lethality screen and drug targeting. Here we have conducted the study for genetic interaction between uncharacterized YDR131C and ATG1 gene representing both specific and non-specific protein degradation pathways. The single and double gene knockout strains of YDR131Cand ATG1 genes were constructed in the BY4741 genetic background and analysed for growth fitness. The strains were also evaluated for cellular growth response in presence of hydroxyurea (HU), methyl methane sulfonate (MMS), and hydrogen peroxide (H2O2) stress causing agents by spot assay. The ydr131c{Delta}atg1{Delta} showed the synthetic growth defect phenotype with floc formation in rich medium which showed floc disruption in presence of EDTA. The ydr131c{Delta}atg1{Delta} cells showed the sensitivity to stress agents HU, MMS, and H2O2 when compared with ydr131c{Delta}, atg1{Delta}, and WT cells.. Based on the observations, we report that YDR131C and ATG1 functions in parallel pathways for growth fitness and cellular growth response to stress agents. Interestingly this study also revealed the crosstalk between ubiquitination and autophagy pathways. The defects in both the pathways could lead to synthetic growth defects which may have implication for the precision medicine initiatives.

PCOS is the most common hormonal disorder and cause of infertility in females of reproductive age. The symptoms and their severity vary strongly between particular cases. PCOS is correlated with hormonal, environmental and genetic factors. Complex interactions between genetics and hormonal levels is important to understand the hormonal 31 abnormality and to assess the chance of pregnancy in women with PCOS. The research was conducted on patients in the age of 27+/-5 years treated in the 33 Gynecology and Oncology Clinic of CMUJ. The research group - PCOS patients (P) n=62. The control group - (C) n=45. The venous blood was collected in volume of 2 ml centrifuged for 15 min at 1400 rpm. Serum was aspirated to 1.5 ml Eppendorf tubes. The ELISA method was used. The statistical analysis revealed significant differences in the level of selected factors 38 between the two groups at p <0.01. FSH [IU/ml]: P 5,10 ({+/-}1,64) vs K 8,96 ({+/-}6,15) LH [ IU/ml]: P 8,59 ({+/-}6,79) vs K 11,0 ({+/-}6,15) AMH [ng/ml]: P 4,06 ({+/-}2,43) vs K 1,47 ({+/-}2,14). AMH levels in the PCOS group did not show a significant difference in correlation with age. Obese and overweight women in both 42 groups had significantly different levels of AMH compared with normal-weight women. Furthermore, AMH levels were positively correlated with the age of the first period in the PCOS. The studies indicate a high use of the hormones like FSH and AMH in the diagnosis and assessment of ovarian reserve in women with PCOS.

Calcium is crucial in insulin biology and Ca2+ sensor proteins enforced in insulin release and signalling. The neuronal calcium sensor proteins (NCS) such as NCS-1 and VILIP are shown to be involved in insulin secretion from {beta}-pancreatic cells. However, the expression of different NCS proteins in the pancreas and their functional significance and role in pathologies remained unexplored. The present work, through different biophysical methods, presented that NCS proteins interact with insulin. NCS-1, the founder member of NCS family proteins interacts with insulin in a Ca2+ independent manner and Ca2+ enhances the affinity of the interaction. The evolutionarily conserved cryptic EF-hand in NCS proteins was found to be an essential commodity for binding insulin. The presence of Ca2+ binding first EF-hand abolishes the interaction with insulin and suggests the significance of non-functional EF-hand. The fluorescence and circular dichroism (CD) spectroscopy show that insulin interaction induces structural changes in NCS-1, which is demonstrated by size exclusion chromatography and analytical ultra-centrifugation. The autism mutant NCS-1-R102Q relatively retained insulin binding properties but with a significant difference in binding thermodynamics. Considering substantial sequence similarity among different NCS proteins and localisation in the pancreas, we examined the insulin interaction with the neurocalcin delta (NCALD). The NCALD shows metal ion-independent insulin binding and contrary to NCS-1, the Ca2+ abolishes the insulin binding. This highlights the differential regulation of Ca2+ towards insulin interaction in NCS protein. Conclusively the present work highlight that NCS proteins interact with insulin and further investigation would aid to understand the significance of NCS proteins in insulin physiology/pathophysiology and possible new molecular targets in diabetes.

In this paper, ACE2 gene of pigs was cloned and the purified protein was obtained via the prokaryotic expression system. Polyclonal antibody of high titer and sensitivity was obtained using Wastar rats immunization method and is then used to determine of the expression of ACE2 using immunohistochemistry. The sequence of ACE2 in pigs covered 2418 nucleotides and coded 805 amino acid (aa) residues. Sequence homology analysis showed that the ACE2 sequence in pigs is highly conserved among species at the nucleotide and amino acid levels. Genetic evolution analysis revealed that ACE2 gene in pigs has the shortest genetic distance with that in goats while residing in a totally different branch from that in zebra fishes. Analysis of protein structure predicted that ACE2 protein is a transmembrane secreted protein with high hydrophilicity, containing a signal peptide sequences locating between 1aa to 17aa. The ACE2 fusion protein expressed (under the induction with 1.0 mmol/L IPTG for 10 h) was of approximately 100 kDa and mainly existed in inclusion body. Wastar rats immunization showed that the titer of the anti-ACE2 antiserum in rats was 1: 3200. Western blot showed that the antibody binds specifically. Immunohistochemistry showed that the ACE2 protein was expressed in all major tissues of pigs. It is the first time that polyclonal antibody of ACE2 in pigs was obtained and the expression of ACE2 was confirmed. These results will provide a basis for investigating on ACE2s biological activity in pigs.

The early studies on chicken embryos revealed that exposition to 4-oxo-L-proline resulted in the explicit increase in 4-hydroxy-L-proline content in their tissues. In 1962, 4-oxo-L-proline reductase, an enzyme responsible for the reduction of 4-oxo-L-proline, was partially purified from rabbit kidneys and characterized biochemically, but only recently the molecular identity of the enzyme has been unveiled in our laboratory. The present investigation reports the purification, identification as well as biochemical characterization of 4-oxo-L-proline reductase. The enzyme was purified from rat kidneys about 280-fold. Following mass spectrometry analysis of the purified protein preparation, the mammalian cytosolic type 2 (R)-{beta}-hydroxybutyrate dehydrogenase (BDH2) emerged as the only meaningful candidate for the reductase. Rat and human BDH2 were expressed in E. coli, purified, and shown to catalyze the reversible reduction of 4-oxo-L-proline to cis-4-hydroxy-L-proline, as confirmed by chromatographic and mass spectrometry analysis. Specificity studies carried out on both enzymes showed that 4-oxo-L-proline was the best substrate, particularly the human enzyme acted with 9400-fold higher catalytic efficiencies on 4-oxo-L-proline than on (R)-{beta}-hydroxybutyrate. Finally, HEK293T cells efficiently metabolized 4-oxo-L-proline to cis-4-hydroxy-L-proline and simultaneously accumulated trans-4-hydroxy-L-proline in the culture medium, suggesting that 4-oxo-L-proline is most likely an inhibitor of trans-4-hydroxy-L-proline metabolism in human cells. We conclude that BDH2 is mammalian 4-oxo-L-proline reductase that converts 4-oxo-L-proline to cis-4-hydroxy-L-proline, and not to trans-4-hydroxy-L-proline as currently thought, and hypothesize that the enzyme may be considered as a potential source of cis-4-hydroxy-L-proline in mammalian tissues.

The R2TP is a multimeric protein complex consists of RUVBL1, RUVBL2, PIH1D1, and RPAP3, and it is known to functions as a specialized co-chaperone. We hypothesize that PIH1D1 recognizes p53 and stabilizes it via R2TP complex. Upon successful completion of this study, innovative mechanism has been found for the interaction and stabilization of p53 and hence govern the cell cycle. Upon interaction between p53 and PIH1D1 protein, p53 is stabilized by PIH1D1 protein, without affecting its C-terminal domain. We have also observed that p53 protein levels were affected after the alteration in expression levels of PIH1D1. Based on the finding, we suggest that the R2TP complex stabilizes and regulates P53. Therefore, this novel method will work as a flashpoint to restore the function of p53 in cancer cells, controlling cancer and cell cycle progression.

Sodium-bile acid cotransporter, also denominated sodium-taurocholate cotransporting polypeptide (NTCP) is an integral membrane protein with multiple hydrophobic transmembrane domains. The third extracellular domain of NTCP presents a stretch of nine aminoacids (KGIVISLVL) that is characterized by pronounced hydrophobicity and serves as receptor for a protein, preS1, showing the hydrophobic epta-peptide sequence NPLGFFP. Vitamin D-binding protein macrophage activating factor (DBP-MAF) is a multifunctional protein that is characterized by two hydrophobic regions able to bind fatty acids and vitamin D, respectively. Here we demonstrate that NTCP and DBP-MAF show significant sequence similarities as far as hydrophobic stretches of aminoacids are concerned. Alignment of the sequence of seven aminoacids preceding the 157-KGIVISLVL-165 stretch of NTCP shows four aminoacids that are identical to those of the corresponding sequence of DBP-MAF, and two that are conserved substitutions. In addition, in the sequence of DBP-MAF that is aligned with the sequence YKGIVISLVL of NTCP, there are two contiguous negatively charged aminoacids (ED) and, in the preceding epta-peptide sequence, there are three negatively charged aminoacids (D-ED), whereas in the corresponding sequence of NTCP there are only two (D--D) that are not contiguous. This concentration of negatively charged aminoacids may be involved in binding of protein inserts characterized by high density of positively charges residues. The alternating hydrophobic and electrostatic interactions described in this paper may help elucidating the biological roles of these proteins as far as protein-protein interactions are concerned.

IntroductionGestational diabetes mellitus (GDM) is one of the most prevalent complications of pregnancy. In a joint statement released in 2018, the International Federation of Obstetrics and Gynecology (FIGO) and the International Diabetes Federation (IDF) stated that high blood glucose levels during pregnancy have an impact on maternal, newborn, and child health and may contribute to the global burden of type 2 diabetes mellitus and cardiovascular metabolic disorders in the short and long term. ObjectivesThe basic aim of the study is to analyze vitamin B12 in pregnancy and its relationship with maternal BMI and gestational DM. Material and methodsThis cross-sectional study was conducted in THQ Hospital Deepalpur, Pakistan during March 2021 to August 2021. Record gathered from 118 hospitals with the total number of 364 women stated for the study coordinator. As per database record, 11% (41 women) were excluded due to initial trimester spontaneous abortion as well as type 2 diabetes diagnosed in 16; 4% and follow up loss 2; 1%. ResultsMaternal outcomes in pregnant women with type 1 diabetes and those without the disease were evaluated in this study. No maternal mortality occurred within 30 days of delivery in 630 pregnancies with type 1 diabetes. However, pregnant women with type 1 diabetes were usually at a much higher risk of developing adverse maternal events during their pregnancy than women without type 1 diabetes, even after adjusting for age and infant sex or age, infant sex, place of residence, income level, occupation, calendar year, and Charlson comorbidity index. ConclusionIt is concluded type 1 diabetes remains a significant disease threatening pregnant women and their offspring. Clinicians should be aware of this clinical situation.

Protein kinase C (PKC){delta} is a serine/threonine kinase involved in many cellular processes in response to diverse stimuli, including cell proliferation, differentiation, apoptosis, tumor inhibition, and cell migration. PKC{delta} consists of the N terminal regulatory domain and the C terminal catalytic domain, which are linked with a hinge region. An alternative splicing variant of rat PKC{delta} (also known as PKC{delta}III) has been reported, and this PKC{delta} splicing variant (SV) has only the regulatory domain without the catalytic domain. However, its function remains unclear. In this study, we found that PKC{delta} SV induced neurite outgrowth in the absence of nerve growth factor (NGF) in PC12 cells. Immunoblot analysis revealed that ERK was phosphorylated by NGF treatment, but not by PKC{delta} SV induction, indicating that PKC{delta} SV-mediated neurite outgrowth was different from NGF-mediated one. In addition, we showed that PKC{delta} full length and SV increased their mRNA expression after NGF treatment and that PKC{delta} SV was more susceptible to its proteasomal degradation. Our findings provided insights into the role of PKC{delta} SV in neurite outgrowth.

IntroductionPregnancy leads to a state of chronically increased intra-abdominal pressure (IAP) caused by a growing fetus, fluid, and tissue. Increased intra-abdominal pressure is leading to state of Intra-Abdominal Hypertension (IAH) and Abdominal Compartment Syndrome. Clinical features and risk factors of preeclampsia is comparable to abdominal compartment syndrome. Intra-abdominal pressure (IAP) may be associated with the pathogenesis of pregnancy induced hypertension. ObjectivesThe study aimed to determine the antepartum and postpartum IAP levels in women undergoing caesarean delivery (CD) and association between hypertension in pregnancy, and antepartum and postpartum IAP levels in women undergoing caesarean delivery (CD). MethodSeventy pregnant women (55 normotensive, 15 hypertension in pregnancy) undergoing antepartum, non-emergency CD, had their intravesical pressure measured before and after the CD, the intravesical pressure measurements obtained with the patient in the supine position were considered to correspond to the IAP. Multivariable linear regression models were used to study associations between intraabdominal pressure and baseline characteristics in normotensive pregnancies and hypertensive pregnancies. ResultsIn normotensive pregnancies at mean gestation age of 38 weeks +2days (95%CI 37+6 to 38 +4), mean antepartum IAP was 12.7 mmHg(95%CI 11.6 to 13.8) and the mean postpartum IAP was 7.3 mmHg (95% CI 11.6 to 13.8). Multivariable linear regression models showed hypertension in pregnancy group antepartum IAP positively associated with coefficient value of 1.617 (p= 0.268) comparing with normotensive pregnancy group. Postpartum IAP in hypertension in pregnancy group positively associated with coefficient value of 2.519 (p= 0.018) comparing with normotensive pregnancy group. IAP difference is negatively associated with hypertension in pregnancy (coefficient -1.013, p= 0.179) ConclusionIn normotensive pregnancies at term, the IAP was in the IAH range of the non-pregnant population. Higher Antepartum IAP and Postpartum IAP are associated with hypertension in pregnancy. Reduction of IAP from antepartum period to postpartum period was less with hypertension in pregnancy.

Withdrawal StatementThe authors have withdrawn their manuscript owing to a conflict of interest. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author, Soumendranath Bhakat.

In this paper, we constructed several models of the Insulin Receptor protein(abbreviated INSR) from protein sequences from pathogenic and benign variants of type 2 Diabetes Mellitus patients. Through modeling these variants, we were able to determine which sections of the tertiary structure of the INSR protein were linked to type 2 Diabetes Mellitus. Ultimately, we created a map of the INSR protein and indicated which parts of the protein structure had significant effects on type 2 Diabetes Mellitus. We concluded differences in the charged/polar amino acids on the lower right section of the structure(amino acid numbers 487 and 750) were associated with pathogenic variants, while charged/polar differences on the lower left of the structure(amino acid numbers 669 and 784) had no impact on pathogenicity. We observed several differences in the amino acid chain structure, however they were not unique to the pathogenic variants; they were also seen in the benign variants.

B cell receptor (BCR) mediated activation of nuclear factor {kappa}B (NF-{kappa}B) is key to humoral immunity. CARMA1 (CARD11) is essential for BCR mediated NF-{kappa}B activation by interacting with Bcl10 and MALT1. Besides these two main players, few interaction partners of the CARMA1 complex are known. Here we identified new interaction partners of CARMA1. We generated two rabbit antisera against mouse CARMA1 to immunopurify endogenous CARMA1 from lysates of mouse B cells. Nik-binding protein (NIBP), Ras-GAP SH3 binding protein 2 (G3BP1) and Trk-fused gene (Tfg) were identified by peptide mass fingerprinting in immunopurified CARMA1 complexes. The interaction of Tfg and CARMA1 was confirmed by co-immunoprecipitation and Blue native polyacrylamide gel electrophoresis using the anti CARMA1 and newly generated anti Tfg antibodies. This analysis revealed that CARMA1 formed complexes of 600-1000 kDa. Additionally, Tfg was found in complexes of 500-600 kDa which increased in size to [~]740 kDa upon overexpresssion.

IntroductionGestational diabetes mellitus (GDM) amplified the physiological alterations of maternal serum lipid levels in the third trimester, with higher triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL-C) levels. No studies about the association between maternal lipid levels in the third trimester and the risk of GDM in Vietnamese population. Methoda cross-sectional study on 1022 healthy females with singleton pregnancy delivered at Bach Mai hospital from May 2023 to June 2024. Measure fasting serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides at 28 - 40 weeks of gestation by color enzymatic assays. Assess the association between maternal serum lipid levels with GDM by multivariate logistic regression. ResultsAfter adjusting for maternal age, pre-pregnancy body mass index (BMI), history of GDM, history of macrosomic neonates and family history of diabetes mellitus, every unit elevation of TG level was associated with increased risk of GDM (OR=1.25, 95% CI: 1.07 - 1.47); every unit elevation of LDL-C was associated with decreased risk of GDM (OR=0.61; 95%CI: 0.40 - 0.95). The association of LDL-C was significant in 33-36 weeks group (OR=0.35, 95% CI: 0.14 - 0.86). TG was significantly associated with GDM in 37 - 40 weeks group (OR=1.72; 95% CI: 1.32 - 2.25). To predict GDM, optimal cut-off points of LDL-C were [&le;]3.17 (for the third trimester) and [&le;]3.25 (for 33 - 36 weeks) while the threshold of TG were [&ge;]3.30 (for the third trimester) and [&ge;]3.31mmol/L (for 37 - 40 weeks). ConclusionAmong Vietnamese population, LDL-C and TG were independent associated factors of GDM in the third trimester. Elevated level of TG was a risk factor, whereas low level of LDL-C was a protective factor of GDM.

BackgroundPregnancy, especially in the third trimester, is associated with changes in the fibrinolytic system that supports clot formation and reduces hemorrhagic risk. Imbalance in the system may occur and can be assessed by plasmin generation (PG). Certain factors are known to affect PG. AimTo assess PG and its determinants during pregnancy using plasma D-dimer and plasmin-antiplasmin (PAP) complex levels. MethodsHealthy pregnant women in the third trimester of pregnancy were systematically recruited. Using the ELISA method, venous blood samples were taken to assess D-Dimer and PAP complex plasma levels. IBM Statistical Package for Social Sciences (SPSS) version 21 was used for statistical analysis. ResultsWe studied a total of 41 subjects with a mean age {+/-}SD and gestational age {+/-}SD of 30.68{+/-}4.69years and 34.78{+/-}3.34weeks, respectively. The mean {+/-} SD values of the D-Dimer and PAP complex were 194 {+/-} 24 ng/mL and 175 {+/-} 11 ng/mL, respectively. D-Dimer and PAP complex positively correlated with age, GA, and BMI classification. However, only age was statistically significant (p-value 0.032 and 0.016, respectively). In addition, the multiple linear regression model showed that with every unit increase in age, D-Dimer and PAP complex increased by 2.0 (95% CI 0.4 - 3.6) ng/mL and 0.8 (95% CI 0.1 - 1.5) ng/mL respectively, after controlling for GA and BMI. ConclusionD-Dimer and PAP levels increased with increasing age during the third trimester of pregnancy, showing that the womans age is an independent determinant of PG in the third trimester.

Backgroundanalysis of fetal/placental components of women with gestational diabetes presented a slightly inflammatory profile, compared with non-diabetic pregnant women in previous studies by our group. Leptin, resistin and IL-6 are involved in the inflammatory process while adiponectin can act in anti-inflammatory processes. PurposeSince both obesity and gestational diabetes are associated with inflammatory conditions, through these mediators we seek to evaluate systemic patterns in pregnant women and fetal patterns of this possible inflammation. Materials and MethodsThree adipokines (leptin, resistin and adiponectin) and one cytokine (IL-6) were studied in three different compartments (maternal serum, fetal serum and amniotic membrane culture supernatant). Four pregnant groups were analyzed (eutrophic, overweight, obese and gestational diabetics (GDM)). Maternal and fetal serum and amnion membrane biopsies were collected from 20 GDM and 28 normoglycemic subjects (Controls) who underwent elective cesarean sections. ResultsWe found a higher production of IL-6 in the culture supernatant of the amniotic membrane of obese pregnant women and more significantly in pregnant women with gestational diabetes. We did not observe correlation between the levels of mediators detected in the three compartments (mother serum, fetal serum and culture supernatant of amniotic membrane). ConclusionMainly in the amniotic membrane of pregnant women with GDM, a slight increase in inflammatory markers was observed.

ObjectiveMaternal mortality remains a global health concern in developing countries that are also affected by HIV infection. Complement components are anaphylatoxin that mediate several growth factors necessary during pregnancy. An extensive stimulation of the complement system contributes to the pathogenesis of preeclampsia; hence its inhibition facilitates a successful pregnancy. The study evaluated the expression of complement components C2 and C5a in HIV and the association with preeclampsia. Materials and MethodsSerum samples were collected from 76 pregnant women of which 38 were preeclamptic and 38 normotensive pregnant. The participants were further stratified according to HIV infection status. Bio-Plex multiplex immunoassay method was used to quantify serum concentration of C5a and C2 complement components. ResultsThe C2 complement concentration was not significantly different between preeclamptic and normotensive pregnant women, irrespective of HIV status as well as pregnancy type. However, based on preeclamptic vs normotensive pregnancy type, the expression of C5a was significantly different (p = 0.05). The C5a levels were downregulated in preeclampsia compared to normotensive women, irrespective of HIV status. Both C2 and C5a concentrations did not differ across all study groups. ConclusionThis novel study reports a loss of regulation of complement activation shown by the downregulation of C5a in preeclamptic compared to normotensive pregnant women, regardless of HIV status. Complement dysregulation affects the host innate defence, and as a consequence, intensifies placental and fetal injury. Moreover, HIV status did not influence the expression of both C5a and C2, irrespective of pregnancy type, this may be attributed to Highly Active Antiretroviral Therapy.

ObjectiveWe aimed to phenotype the Indian PCOS population based on their etiology for an effective treatment regimen. DesignRetrospective analysis of biochemical data. SettingPCOS clinics in Tamil Nadu, India Population or SampleGirls and women in age group 18 to 30 diagnosed as PCOS by RC. MethodThe statistical analysis was done using two-way cluster analysis function of SPSS v.22 to identify the phenotypes and the resolving biochemical parameter. Also, the population was segregated into three cohorts based on their age for further analysis. Main outcome measureEndocrine parameters like LH, FSH, estradiol, testosterone and thyroid profile. Biochemical parameters like complete lipid profile, blood glucose and insulin fasting. Body Mass Index (BMI). ResultsThe statistical analysis reported two phenotypes among the Indian PCOS population, segregated based on their LH: FSH ratio. The phenotype with LH: FSH >2, had a hormonal imbalance and may have its etiology from Hypothalamus - Pituitary - Ovarian axis. The phenotype with LH: FSH < 2 had significant markers indicating the incidence of metabolic syndrome and may follow an insulin - dependent pathway for PCOS manifestation. ConclusionThe PCOS population needs a comprehensive screening before deciding on a treatment regimen. All the PCOS patients need to be recommended to follow an active lifestyle since 80% of them are predisposed to a metabolic syndrome in their later ages.