A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy.

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy

Abstract Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumor explants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways.

Early onset of chemotherapy evasion is a therapeutic challenge. Chemotherapy-induced upregulation of stem cell markers imparts invasiveness and metastatic property to the resident tumor. The efficacy of Kaempferol in attenuating epithelial to mesenchymal transition has earlier been established in the breast cancer cell. In our study population, progression-free survival was observed to be statistically more significant in post-NACT low-grade tumors than the high-grade tumors. Further, in post-NACT TNBCs, high-grade tumors showed a preponderance of strong nuclear p53 expression and very low expression of Caspase 3, indicating that, altered p53 expression predisposes these tumors to apoptosis escape and up-regulation of stemness markers. Herein, we report the robust efficacy of Kaempferol on ex-vivo grown breast tumors, derived from post-NACT TNBC patients, through downregulation of nuclear p53, CD44, ALDH1, NANOG, MDR1, Ki67, BCL2 and upregulation of Caspase 3. Such tumors also showed concurrent deregulated RNA and protein expression of CD44, NANOG, ALDH1 and MDR1 with upregulation of Caspase 3 and cleaved Caspase 3, upon Kaempferol treatment. Validation of efficacy of the treatment dosage of Kaempferol through immunophenotyping on MDA-MB-231, suggested that Kaempferol at its IC-50 dosage was effective against CD44 and CD326 positive breast cancer through deregulating their expression. Protein-protein interaction network through STRING pathway analysis and co-expression study of candidate proteins showed the highest degree of co-expression of p53 and KI-67, CD44, NF- kappaB, ALDH1, NANOG, MDR1, and BCL2. Thus, potentially targetable oncogenic protein markers, that are susceptible to downregulation by Kaempferol, provides insight into biomarker-driven therapeutic approaches with it.

Deregulation of the CD44-NANOG-MDR1 associated chemoresistance pathways of breast cancer stem cells potentiates the anti-cancer effect of Kaempferol in synergism with Verapamil.

Chemoresistance is an imminent therapeutic challenge for breast cancer. Previous evidence suggests that breast cancer stem cells (BCSC) develop resistance through upregulation of stemness and chemo-evasion markers viz. SOX2, OCT4, NANOG, MDR1 and CD44, following anticancer chemotherapeutic treatments. Early studies suggest an inhibitory role of Kaempferol in BCSC propagation through downregulation of epithelial to mesenchymal transition. We hypothesized that the pathway involved in chemoresistance could be effectively addressed through Kaempferol (K), alone or in combination with Verapamil (V), which is an inhibitor of MDR1. We used K in combination with V, in multiple assays to determine if there was an inhibitory effect on BCSC. Both K and KV attenuated pH-dependent mammosphere formation in primary BCSC and MDA-MB-231 cells. RNA and protein (immunocytochemistry, western blot) expression of candidate markers viz. SOX2, OCT4, NANOG, MDR1 and CD44 were carried out in the presence or absence of candidate drugs in ex-vivo grown primary BCSC and MDA-MB-231 cell line. Immunoprecipitation assay, cell cycle analysis was carried out in MDA-MB-231. Our candidate drugs were not only anti-proliferative, but also downregulated candidate genes expression at RNA and protein level in both settings, with more robust efficacy in KV treatment than K; induced G2/M dependent cell cycle arrest, and interrupted physical association of CD44 with NANOG as well as MDR1 in MDA-MB-231. In primary tumor explant but not in adjacent normal tissue, our candidate drugs K and KV induced robust γH2AX expression. Thus, our candidate drugs are effective in attenuating BCSC survival.

Curved colloidal crystals of discoids at near-critical liquid-liquid interface.

The assembly of disc-shaped particles at curved liquid-liquid interfaces was studied by using confocal microscopy. The interface is formed by a phase-separating critical liquid mixture of 2,6-lutidine and heavy water, where the colloids spontaneously assembled forming a dome. The novelty of this system is three-fold. First, the domes can be constructed and annihilated remotely and reversibly, which allows dynamic control of the colloidal assembly. Second, the effect of curvature can be investigated by analyzing domes of different radii ranging from 5 µm to 125 µm. Third, the slow dynamics due to hydrodynamic interaction among the particles can be utilized to investigate the time-evolution of defect morphology. Unlike the widely studied repulsive colloids, the interparticle potential near the critical point has an attractive component. I contrasted the packing and defects morphology of a solid-like and liquid-like dome differing in particle number density. In the solid-like dome, a chain of 5- and 7-fold coordinated particles was observed. The analysis of trajectories showed that particles were bound in a potential well of a depth of about ten times the thermal energy, which matched well with the calculation of the pair-potential by considering the attractive critical Casimir force among the particles. In the liquid-like dome, 6-fold particles separated by clusters of 5- and 7-coordinated particles were observed, which is suggestive of liquid-solid coexistence. The uniqueness of this system will open up a new research avenue to investigate the effect of varying curvature on the crystallization, defects, and phase diagram of colloidal assemblies.

Brownian Diffusion of Individual Janus Nanoparticles at Water/Oil Interfaces.

Janus nanoparticles could exhibit a higher interfacial activity and adsorb stronger to fluid interfaces than homogeneous nanoparticles of similar sizes. However, little is known about the interfacial diffusion of Janus nanoparticles and how it compares to that of homogeneous ones. Here, we employed fluorescence correlation spectroscopy to study the lateral diffusion of ligand-grafted Janus nanoparticles adsorbed at water/oil interfaces. We found that the diffusion was significantly slower than that of homogeneous nanoparticles. We carried out dissipative particle dynamic simulations to study the mechanism of interfacial slowdown. Good agreement between experimental and simulation results has been obtained only provided that the flexibility of ligands grafted on the nanoparticle surface was taken into account. The polymeric ligands were deformed and oriented at an interface so that the effective radius of Janus nanoparticles is larger than the nominal one obtained by measuring the diffusion in bulk solution. These findings highlight further the critical importance of the ligands grafted on Janus nanoparticles for applications involving nanoparticle adsorption at an interface, such as oil recovery or two-dimensional self-assembly.

Diffusion of nanoparticles within a semidilute polyelectrolyte solution.

We studied the diffusion of charged gold nanoparticles within a semidilute solution of weakly charged polyelectrolyte, polyacrylic acid (PAA) of high molecular weight (Mw = 106 g mol-1) by using fluorescence correlation spectroscopy (FCS). Nanoparticle size (d) was varied between 5 nm to 40 nm and PAA volume fraction (φ) in water ranged from about 8φ* to 33φ*, where φ* is the overlap volume fraction. The reduced diffusion coefficient - defined as -D/Do, where D is the diffusion coefficient in PAA solution and Do is that in neat water - has a weak dependence on the particle size. D follows a power law of the form ∼φ-0.5, which can be explained by a mean-field hydrodynamic theory in porous medium. Additional, rheology measurements showed a zero shear rate viscosity and shear thinning, which are typical of high molecular weight polyelectrolytes.

SMAR1 favors immunosurveillance of cancer cells by modulating calnexin and MHC I expression.

Down-regulation or loss of MHC class I expression is a major mechanism used by cancer cells to evade immunosurveillance and increase their oncogenic potential. MHC I mediated antigen presentation is a complex regulatory process, controlled by antigen processing machinery (APM) dictating immune response. Transcriptional regulation of the APM that can modulate gene expression profile and their correlation to MHC I mediated antigen presentation in cancer cells remain enigmatic. Here, we reveal that Scaffold/Matrix-Associated Region 1- binding protein (SMAR1), positively regulates MHC I surface expression by down-regulating calnexin, an important component of antigen processing machinery (APM) in cancer cells. SMAR1, a bonafide MAR binding protein acts as a transcriptional repressor of several oncogenes. It is down-regulated in higher grades of cancers either through proteasomal degradation or through loss of heterozygosity (LOH) at the Chr.16q24.3 locus where the human homolog of SMAR1 (BANP) has been mapped. It binds to a short MAR region of the calnexin promoter forming a repressor complex in association with GATA2 and HDAC1. A reverse correlation between SMAR1 and calnexin was thus observed in SMAR1-LOH cells and also in tissues from breast cancer patients. To further extrapolate our findings, influenza A (H1N1) virus infection assay was performed. Upon viral infection, the levels of SMAR1 significantly increased resulting in reduced calnexin expression and increased MHC I presentation. Taken together, our observations establish that increased expression of SMAR1 in cancers can positively regulate MHC I surface expression thereby leading to higher chances of tumor regression and elimination of cancer cells.

Nanoparticle Diffusion within Dilute and Semidilute Xanthan Solutions.

We measured the translation diffusion coefficient ( D) of nanoparticles within dilute and semidilute solutions of a semiflexible polymer, xanthan. Our results showed that for particle diameters ( d) of 5 and 10 nm, the obstruction theory can explain the concentration ( c) dependence of D in the dilute regime. Diffusion in semidilute solutions is better explained by additionally considering the modified Darcy flow with the hydrodynamic screening length varying according to κ ≈ c-0.76. The depletion effect is operative for larger particles ( d = 30 nm) within semidilute solutions. We used a scaling relation for the depletion layer thickness δ ≈ ξν, where ξ is the static correlation length and the exponent ν ≈ 0.42 that can explain our data. This is in contrast with a flat surface, where the exponent is expected to be 1. Our results showed that in the situation, when the polymer network relaxation is much slower compared to the diffusive time-scale of particles, no single theory is capable to describe the concentration and size dependence of particle mobility.

Scorpion Venom-Toxins that Aid in Drug Development: A Review.

Scorpion venom components have multifaceted orientation against bacterial, viral, fungal infections and other neuronal disorders. They can modulate the ion channels (K+, Na+, Cl-, Ca2+) of our body and this concept has been hypothesized in formulating pharmaceuticals. The triumphant achievement of these venom components as formulated anticancer agent in Phase I and Phase II clinical trials allure researchers to excavate beneficial venom components prohibiting DNA replication in malignant tumor cells. This review brings forth the achievements of Science and Technology in classifying the venom components as therapeutics and further application in drug product development.

An insight into metastasis: Random or evolving paradigms?

Mechanical or fostered molecular events define metastatic cascade. Three distinct sets of molecular events characterize metastasis, viz invasion of extracellular matrix; angiogenesis, vascular dissemination and anoikis resistance; tumor homing and relocation of tumor cells to selective organ. Invasion of extracellular matrix requires epithelial to mesenchymal transition through disrupted lamellopodia formation and contraction of actin cytoskeleton; aberration of Focal adhesion complex formation involving integrins and the extracellular matrix; degradation of extracellular matrix by matrix metalloproteases; faulty immune surveillance in tumor microenvironment and an upregulated proton efflux pump NHE1 in tumors. Vascular dissemination and anoikis resistance depend upon upregulation of integrins, phosphorylation of CDCP1, attenuated apoptotic pathways and upregulation of angiogenesis. Tumor homing depends on recruitment of mesenchymal stem cells, expression on chemokines and growth factors, upregulated stem cell renewal pathways. Despite of many potential challenges in curbing metastasis, future targeted therapies involving immunotherapy, stem cell engineered and oncolytic virus based therapy, pharmacological activation of circadian clock are held promising. To sum up, metastasis is a complex cascade of events and warrants detailed molecular understanding for development of therapeutic strategies.

Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion protein in chronic myeloid leukemia.

BACKGROUND: Philadelphia chromosome, a hallmark of chronic myeloid leukemia (CML), plays a key role in disease pathogenesis. It reflects a balanced reciprocal translocation between long arms of chromosomes 9 and 22 involving BCR and ABL1 genes, respectively. An accurate and reliable detection of BCR-ABL fusion gene is necessary for the diagnosis and monitoring of CML. Previously, many technologies, most of which are laborious and time consuming, have been developed to detect BCR-ABL chimeric gene or chromosome. METHODS: A new flow cytometric immunobead assay was used for detection of BCR-ABL fusion proteins and applicability, sensitivity, reliability, efficacy and rapidity of this method was evaluated. RESULTS: From February 2009 to January 2014, a total 648 CML patients were investigated for the status of BCR-ABL1 protein. Among them, 83 patients were enrolled for comparative study of BCR-ABL1 positivity by three routinely used procedures like karyotyping, and quantitative real time PCR (RT-PCR) as well as immunobead flow cytometry assay. BCR-ABL protein analysis was found consistent, more sensitive (17% greater sensitivity) and reliable than the conventional cytogenetics, as flow cytometry showed 95% concordance rate to RT-PCR. CONCLUSION: BCR-ABL fusion protein assay using a new flow cytometric immunobead might be useful in the diagnosis and monitoring CML patients.

From molecular insight to therapeutic strategy: The holistic approach for treating triple negative breast cancer.

Aim of the present study was to analyze the molecular pathogenesis of TNBC, therapeutic practice, challenges, and future goals in treatment strategies. Based on the alterations of distinct pathways, Lehmann's subgroups of TNBCs were further categorized. Those with defective DNA damage repair and replication pathways, viz. Basal Like 1 & 2 (BL1, BL2) were found susceptible to DNA intercalating drugs while those with upregulated cell signalling & motility (mesenchymal (M), mesemchymal stem like (MSL)), cell survival (BL2, M, MSL), angiogenesis (BL2, MSL), T cell signalling (Immunomodulatory/IM) pathways required targeted therapies. Our Meta-analysis categorized 12 randomized previous trial cases, solely under the following drug regimens: [1] DNA destabilizers, [2] PARP inhibitors, [3] Microtubule stabilizers, [4] Angiogenesis inhibitors, [5] Antimetabolite, [6] T cell targeted therapy; as single or combinational therapy. Best therapeutic efficacies of DNA destabilizers with angiogenesis inhibitors in combination than monotherapy with either (OR: 5.011-7.286; p value<0.001) indicated a significant prevalence of BL1 type TNBCs in populations. Statistical significance with antimetabolites as combination therapy (OR: 2.343; p value: 0.018) and not with microtubule stabilizer (OR: 0.377) were observed. Thus, for best ORR in TNBC, personalized medicine should be the therapeutic choice for the clinicians.

Determinants of lymph node status in women with breast cancer: A hospital based study from eastern India.

BACKGROUND & OBJECTIVES: Number of metastatic lymph nodes has a strong prognostic value in the course of breast cancer treatment, morbidity and mortality. This study was undertaken to determine the association between axillary lymph node metastasis and several variables such as age, tumour size, grade, lymphovascular invasion, oestrogen and progesterone receptor expression and HER2/neu status in patients with breast cancer. METHODS: In this study 426 (with complete information on study variables) patients with breast cancer on treatment during March 2010 to December 2013, were analyzed. TNM (tumour node matastasis) staging was evaluated. The histological grading of tumours was done according to modified Bloom-Richardson Grading System. The immunophenotype of the tumour was determined as the expression of oestrogen (ER) and progesterone (PR) receptors and Her0 2/neu status. Univariate and multivariate analyses were carried out to determine the independent predictors of metastatic lymph node. RESULTS: Among the studied patients, 44.36 per cent (189 of 426) of the patients had nodal metastases. t0 umour histology, tumour grade, size and lympho-vascular invasion were related with node positivity. On univariate analysis, age, menopause, hormone receptor status did not relate with the node metastasis. Age, tumour grade, tumour size, lympho-vascular invasion and HER2/neu expression was likely to be associated with the number of lymph node metastasis. INTERPRETATION & CONCLUSIONS: The lymph node status was associated with clinical stage, tumour grade, tumour histology and HER2/neu status. t0 hese factors may be used for better management of such patients.

Mugineic acid, active ingredient of wheat grass: an oral novel hexadentate iron chelator in iron overloaded diseases.

Iron chelation therapies are required for the treatment of iron overloaded patients; nonetheless, their side effects are also well known. We have evaluated iron-chelating activity of wheat grass extract (WHE) and its purified compound, mugineic acid in murine model with phenylhydrazine (PHZ) and dextran induced acute and chronic iron overload conditions. PHZ and dextran treatment induced acute and chronic iron overload condition in mice, respectively, as indicated by increased serum and tissue iron in both cases. Iron overload was also accompanied with haemosiderosis in tissues (liver and spleen). These PHZ and dextran -: treated mice were orally treated with either crude WHE or purified mugineic acid. The efficacy of mugineic acid and WHE was compared with the potent oral iron chelator ICL670 (Exjade). PHZ and dextran treatment followed by oral administration of WHE or mugineic acid significantly checked the rise of serum/plasma levels of iron as well as tissue iron and also, haemosiderosis in tissues. The results are highly comparable with known iron chelator ICL670. WHE and purified mugineic acid, both seem to have significant prospect to be the cheap, non-toxic, hexadentate and oral therapeutic agents to prevent or alleviate toxic iron overload in patients.

Evaluating the morphology of erythrocyte population: An approach based on atomic force microscopy and flow cytometry.

Erythrocyte morphology is gaining importance as a powerful pathological index in identifying the severity of any blood related disease. However, the existing technique of quantitative microscopy is highly time consuming and prone to personalized bias. On the other hand, relatively unexplored, complementary technique based on flow cytometry has not been standardized till date, particularly due to the lack of a proper morphological scoring scale. In this article, we have presented a new approach to formulate a non-empirical scoring scale based on membrane roughness (R(rms)) data obtained from atomic force microscopy. Subsequently, the respective morphological quantifier of the whole erythrocyte population, commonly known as morphological index, was expressed as a function of highest correlated statistical parameters of scattered signal profiles generated by flow cytometry. Feed forward artificial neural network model with multilayer perceptron architecture was used to develop the intended functional form. High correlation coefficient (R(2) = 0.95), even for model-formulation exclusive samples, clearly indicates the universal validity of the proposed model. Moreover, a direct pathological application of the proposed model has been illustrated in relation to patients, diagnosed to be suffering from a wide variety of cancer.

Role of membrane cholesterol and lipid peroxidation in regulating the Na+/K+-ATPase activity in schizophrenia.

BACKGROUND: Na+/K+-ATPase (NKA) activity is compromised in several neuropsychiatric disorders. Oxidative stress and membrane lipid composition play important roles in regulating NKA activity. AIMS: The present study was undertaken to evaluate the effects of oxidative stress-induced membrane lipid damage and membrane cholesterol composition on NKA pump activity in schizophrenia. SETTINGS AND DESIGN: It was a hospital-based, cross-sectional, observational study in 49 cases and 51 controls for 1 year. MATERIALS AND METHODS: NKA pump activity in red blood cell membrane, serum levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC) adducts, and cholesterol were measured by standard spectrophotometric techniques in newly diagnosed schizophrenia patients by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. Membrane cholesterol was analyzed by chloroform and isopropanol extraction followed by measuring the cholesterol concentration by spectrophotometric technique. STATISTICAL ANALYSIS AND RESULTS: Mean values for NKA pump activity, membrane cholesterol level, and serum cholesterol levels were significantly lower in the case group (P < 0.001). The activity of NKA pump was found to be directly correlated to membrane cholesterol level rather than with the serum cholesterol values. Although the NKA pump activity showed inverse relationship with the serum values of TBARS and PC products both, on multiple linear regression analysis, it was found to be significantly positively dependent on the membrane cholesterol (ß = 0.268, P = 0.01) and negatively dependent on the serum TBARS (ß = -0.63, P < 0.001) levels only. CONCLUSION: Reduced membrane cholesterol and oxidative stress-induced damage to membrane lipids play crucial roles in decreasing the NKA activity in schizophrenia. Hence, for a better prognosis and treatment, measures are required to maintain optimum levels of cholesterol in neuronal tissues along with a proper control on oxidative stress.

The Potential Utility of Acceptance and Commitment Therapy (ACT) for Reducing Stress and Improving Wellbeing in Cancer Patients in Kolkata.

As soon as a patient comes to know that he/she has cancer, the stress starts and psychological intervention is required. The authors assessed how well a cancer patient can manage stress over the course of the psychological intervention. Data was collected among 107 patients during pre and post intervention and at 2 months follow-up. Intervention was required to measures include acceptance of the disease, managing stress, well -being, and meaning of life. Finally, effects of acceptance and commitment therapy (ACT) were defined in acceptance measured in terms of a significant difference between pre and post intervention scores in the meaning of life and the acceptance level. This acceptance and commitment therapy can be an effective intervention approach for cancer patients that increases acceptance regarding disease and simultaneously leads to improvement in the meaning of life.