Transporter targeted-carnitine modified pectin-chitosan nanoparticles for inositol hexaphosphate delivery to the colon: An in silico and in vitro approach.

Orally targeted delivery systems have attracted ample interest in colorectal cancer management. In this investigation, we developed Inositol hexaphosphate (IHP) loaded Tripolyphosphate (Tr) crosslinked Pectin (Pe) Chitosan (Ch) nanoparticles (IHP@Tr*Pe-Ch-NPs) and modified them with l-Carnitine (CE) (CE-IHP@Tr*Pe-Ch-NPs) to improve uptake in colon cells. The formulated CE-IHP@Tr*Pe-Ch-NPs displayed a monodisperse distribution with 219.3 ± 5.5 nm diameter and 30.17 mV surface charge. Cell-line studies revealed that CE-IHP@Tr*Pe-Ch-NPs exhibited excellent biocompatibility in J774.2 and decreased cell viability in DLD-1, HT-29, and MCF7 cell lines. More cell internalization was seen in HT-29 and MCF7 due to overexpression of the OCTN2 and ATB0,+ transporter (CE transporters) compared to DLD-1. The cell cycle profile, reactive oxygen species, apoptosis, and mitochondrial membrane potential assays were performed to explore the chemo-preventive mechanism of CE-IHP@Tr*Pe-Ch-NPs. Moreover, the in-silico docking studies revealed enhanced interactive behavior of CE-IHP@Tr*Pe-Ch-NPs, thereby proving their targeting ability. All the findings suggested that CE-IHP@Tr*Pe-Ch-NPs could be a promising drug delivery approach for colon cancer targeting.

Immunohistopathological Study of Papillary Squamotransitional Carcinoma of Uterine Cervix.

INTRODUCTION: Papillary squamotransitional cell carcinoma (PSTCC) arising from the uterine cervix is a distinctive histomorphological subtype of squamous cell carcinoma (SCC) not otherwise specified (NOS) of cervical epithelial tumors. AIM: The present study was undertaken to study the histopathological features and immunoexpression of CK7, CK20, p53 and Ki-67 in PSTCC of the cervix. MATERIALS AND METHODS: This study included 43 cases of PSTCC of cervix. A technique of manual tissue array was employed along with IHC staining of entire section in some cases. The expression pattern of CK7, CK 20, p53 and Ki67 in PSTCC was studied and clinico-pathological correlation of various parameters with IHC expression of CK7 and CK20 was observed. Results were subjected to statistical analysis and were considered significant when the p-value was less than 0.05. RESULTS: Out of 43 PSTCC cases, there were 38 squamotransitional type and 5 papillary type. Histomorphologically, all the cases studied were having fused papillae with rounded contours and fibrovascular cores with highest number of cases having intermediate cell type morphology (86%). Stromal invasion was seen in 74.4% of cases. Koilocytosis were seen in 39.3% of cases. Thirty-two cases showed CK7 immunopositivity (+) and CK20 immunonegativity (-), nine cases were both CK7 and CK20 - and two cases were CK7- and CK20+. Among them 90.7% cases were p53 positive and all cases were positive for Ki67 immunostaining with highest number of cases showing moderate proliferative activity (74.4%); followed by nine cases showing high (20.93%) and two cases showing low proliferative activity (4.65%). CONCLUSION: The distinct histomorphology and CK7/CK20 immnunoprofile of PSTCC along with Ki67 and p53 could help in arriving at an accurate diagnosis as well predicting its biological behavior.

Unleashing the Potential of Benincasa hispida Peel Extract: Synthesizing Selenium Nanoparticles with Remarkable Antibacterial and Anticancer Properties.

In this study, we successfully synthesized selenium nanoparticles (P-SeNPs) using an environment-friendly approach. This method involves utilizing the aqueous peel extract of Benincasa hispida (ash gourd) in combination with selenium salt. Through our innovative procedure, we harnessed the impressive bio-reduction capabilities, therapeutic potential, and stabilizing attributes inherent in B. hispida. This results in the formation of P-SeNPs with distinct and noteworthy qualities. Our findings were thoroughly substantiated through comprehensive characterizations employing various techniques, including ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier transform infrared spectroscopy (FTIR). The nanoparticles exhibited a spherical shape, considerable size (22.32 ± 2 nm), uniform distribution, and remarkable stability (-24 mV), all of which signify the effective integration of the phytoconstituents of B. hispida. Furthermore, P-SeNPs displayed robust antibacterial efficacy against pathogenic bacterial strains, as indicated by their low minimum inhibitory concentration values. Our research also revealed the remarkable ability of P-SeNPs to fight cancer, as demonstrated by their impressive IC50 value of 0.19 µg/mL against HeLa cells, while showing no harm to primary human osteoblasts, while simultaneously demonstrating no toxicity toward primary human osteoblasts. These pivotal findings underscore the transformative nature of P-SeNPs, which holds promise for targeted antibacterial treatment and advancements in cancer therapeutics. The implications of these nanoparticles extend to their potential applications in therapies, diagnostics, and various biomedical contexts. Notably, the environmentally sustainable synthesis process and exceptional properties established this study as a significant milestone in the field of nanomedicine, paving the way for a more promising and health-enhancing future.

A descriptive study of policy and system-level interventions to address cancer survivorship issues across six United States health systems.

PURPOSE: To describe policy and system-level interventions with potential to improve cancer care at six sites. METHODS: In 2016, six institutions received foundation support to develop unique multi-component interventions aimed at improving cancer care for underserved populations. These organizations, located across the United States, participated in a cross-site evaluation to assess the overall initiative impact and to identify potentially promising policy and system-level solutions for dissemination and broader implementation. A health system and policy tracking tool was developed to collect data from each site and included a description of their efforts, strategies employed, and changes achieved (e.g., new policies, clinical protocols). Tracking tool data were analyzed using rapid qualitative analyses and a matrix approach. Semi-structured interviews were conducted with site leaders (N = 65) and were analyzed by thematic analysis. RESULTS: Sites reported 20 system and policy efforts, which resulted in improvements to electronic health records and telehealth strategies, changes to hospital/health system policies, and standardized clinical protocols/guidelines, among others. Efforts were aimed at: (1) coordinating care across multiple providers, supported by patient navigators; (2) expanding psychosocial and supportive care; (3) improving patient-provider communication; and (4) addressing barriers to accessing care. Interview analyses provided insights into successful strategies, challenges, and implications of the COVID-19 pandemic on cancer care. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Despite advances in diagnosis and treatment, cancer care remains inequitable. System-level improvements aimed at eliminating common barriers faced by underserved populations offer opportunities to improve the delivery of equitable, effective, and efficient care.

A rare case of primary giant myxoid liposarcoma of the pericardium.

Primary pericardial neoplasms account for 6.7-12.8% of all primary tumors arising in the cardiac region. Pericardial tumors are most likely to be metastatic and are an extension of the primary tumors from the surrounding structures. Sarcomas of the pericardium are rare. Myxoid liposarcoma (ML) represents about 5% of all the soft-tissue sarcomas in adults. They are usually located in the deep soft tissues of the extremities. There have been less than 20 cases of pericardial liposarcomas reported on PubMed since 1973. Here, we present a rare case of primary giant pericardial myxoid liposarcoma (ML) in a 46-year-old female diagnosed on frozen section and later was confirmed histopathologically.

Reaching Populations to Address Disparities in Cancer Care Delivery: Results From a Six-Site Initiative.

BACKGROUND: Large segments of the US population do not receive quality cancer care due to pervasive and systemic inequities, which can increase morbidity and mortality. Multicomponent, multilevel interventions can address inequities and improve care, but only if they reach communities with suboptimal access. Intervention studies often underenroll individuals from historically excluded groups. METHODS: The Alliance to Advance Patient-Centered Cancer Care includes 6 grantees across the United States who implemented unique multicomponent, multilevel intervention programs with common goals of reducing disparities, increasing engagement, and improving the quality of care for targeted populations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework informed the evaluation efforts across sites. Each Alliance site identified their intended populations, which included underrepresented minorities (eg, Black and Latinx persons), individuals who prefer a language other than English, and rural residents. We evaluated the demographic characteristics of participants to determine program reach. RESULTS: Between 2018 and 2020, a total of 2,390 of 5,309 potentially eligible participants were enrolled across the 6 sites. The proportion of enrolled individuals with selected characteristics included 38% (n=908) Black adults, 24% (n=574) Latinx adults, 19% (n=454) preferring a language other than English, and 30% (n=717) rural residents. The proportion of those enrolled who were the intended population was commensurate to the proportion with desired characteristics in those identified as potentially eligible. CONCLUSIONS: The grantees met or exceeded enrollments from their intended populations who have been underserved by quality cancer care into patient-centered intervention programs. Intentional application of recruitment/engagement strategies is needed to reach individuals from historically underserved communities.

Association of Race and Area Deprivation With Breast Cancer Survival Among Black and White Women in the State of Georgia.

Importance: Increasing evidence suggests that low socioeconomic status and geographic residence in disadvantaged neighborhoods contribute to disparities in breast cancer outcomes. However, little epidemiological research has sought to better understand these disparities within the context of location. Objective: To examine the association between neighborhood deprivation and racial disparities in mortality among Black and White patients with breast cancer in the state of Georgia. Design, Setting, and Participants: This population-based cohort study collected demographic and geographic data from patients diagnosed with breast cancer between January 1, 2004, and February 11, 2020, in 3 large health care systems in Georgia. A total of 19 580 patients with breast cancer were included: 12 976 from Piedmont Healthcare, 2285 from Grady Health System, and 4319 from Emory Healthcare. Data were analyzed from October 2, 2020, to August 11, 2022. Exposures: Area deprivation index (ADI) scores were assigned to each patient based on their residential census block group. The ADI was categorized into quartile groups, and associations between ADI and race and ADI × race interaction were examined. Main Outcomes and Measures: Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% CIs associating ADI with overall mortality by race. Kaplan-Meier curves were used to visualize mortality stratified across racial and ADI groups. Results: Of the 19 580 patients included in the analysis (mean [SD] age at diagnosis, 58.8 [13.2] years), 3777 (19.3%) died during the course of the study. Area deprivation index contributed differently to breast cancer outcomes for Black and White women. In multivariable-adjusted models, living in a neighborhood with a greater ADI (more deprivation) was associated with increased mortality for White patients with breast cancer; compared with the ADI quartile of less than 25 (least deprived), increased mortality HRs were found in quartiles of 25 to 49 (1.22 [95% CI, 1.07-1.39]), 50 to 74 (1.32 [95% CI, 1.13-1.53]), and 75 or greater (1.33 [95% CI, 1.07-1.65]). However, an increase in the ADI quartile group was not associated with changes in mortality for Black patients with breast cancer (quartile 25 to 49: HR, 0.81 [95% CI, 0.61-1.07]; quartile 50 to 74: HR, 0.91 [95% CI, 0.70-1.18]; and quartile ≥75: HR, 1.05 [95% CI, 0.70-1.36]). In neighborhoods with an ADI of 75 or greater, no racial disparity was observed in mortality (HR, 1.11 [95% CI, 0.92-1.36]). Conclusions and Relevance: Black women with breast cancer had higher mortality than White women in Georgia, but this disparity was not explained by ADI: among Black patients, low ADI was not associated with lower mortality. This lack of association warrants further investigation to inform community-level approaches that may mitigate the existing disparities in breast cancer outcomes in Georgia.

Determination of Oxaliplatin and Curcumin in Combination via Micellar HPLC and Its Method Validation.

BACKGROUND: A micellar-HPLC method was developed for the determination of oxaliplatin (OHP) and curcumin (CUR) employing a C18 column [4.6 × 250 mm, particle size (dp) = 5 µm] and diode array detector. OBJECTIVE: A rapid, cost-effective, environmentally friendly, time-efficient, easy-to-handle, and safe method was developed. METHODS: The conditions were optimized for the estimation of OHP and CUR: 0.15 M sodium dodecyl sulfate (SDS) in 6% (v/v) pentanol buffered to pH 5.0 with a flow rate of 1.0 mL/min, injection volume of 20 µL, and detection at 325 nm. Different analytical parameters, including linearity, accuracy, precision, robustness, specificity, LOD, and LOQ, were determined in compliance with the International Council on Harmonisation (ICH) guidelines. RESULTS: The LOD (S/N = 3) of OHP was 0.004 µg/mL and for CUR it was 0.005 µg/mL. The calibration curves for OHP and CUR were linear over the range 0.015-10 µg/mL (determination coefficient r2 = 0.9999) and 0.015-10 µg/mL (r2 = 0.9994), respectively. CONCLUSION: The drugs were eluted in <12 min and the developed method was applicable for analyzing multiple samples per day. Moreover, it was determined to be robust and was used to quantify OHP and CUR in mice serum/blood. The method could pave the way for quantitative analysis of these drugs during the development of a pharmaceutical preparation for the treatment of colorectal cancer. HIGHLIGHTS: A simple, cost-effective, eco-friendly HPLC method was developed to simultaneously estimate oxaliplatin and curcumin. The developed method was validated as per the ICH guidelines.

Performance enhancement and optimization of the anammox process with the addition of iron.

This study was conducted to evaluate the performance of anammox reaction on the addition of iron. Iron was added in the form of FeSO4 starting with 2 mg/L (phase I), 5 mg/L (phase II), 8 mg/L (phase III), 10 mg/L (phase IV), 30 mg/L (phase V) and 50 mg/L (phase VI) on the addition of Fe (II) in anammox reactor. The efficiency of ammonia removal increased up to 90% with 5 mg/L of Fe (II) addition as compared to 77% when no Fe (II) was added. As the iron dosing was increased from 10 to 30 mg/L, ammonia removal declined sharply, which recovered slowly at steady-state condition. However, on the addition of 30 and 50 mg/L of Fe (II), the efficiency declined to 55% and 44%, respectively and did not recover. At 5 mg/L Fe (II) the nitrite removal was nearly 80% which declined to 44% at 50 mg/L. This was attributed to low pH values which hindered anammox activity. The mass balance study of nitrogen in the anammox process revealed that gas production was highest at 5 mg/L of Fe (II) conforming that 5 mg/L of Fe (II) is the optimum dose of iron for enhancing anammox reaction.

Identification of Novel Rho-Kinase-II Inhibitors with Vasodilatory Activity.

Small GTPase protein Rho-kinase (ROCK) plays an important role in the pathogenesis of hypertension. Inhibition of ROCK II brings about the biochemical changes leading to vascular smooth muscles relaxation, finally resulting into potent antihypertensive activity. In the quest for potent ROCK-II inhibitors, a ligand-based pharmacophore containing four essential chemical features, namely two hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), and one hydrophobe (HY), was developed and rigorously validated. The pharmacophore was used for virtual screening, and hits retrieved from the National Cancer Institute (NCI) database were sorted on the basis of fit value, estimate value, and Lipinski's violation. Potential feature interaction of hits was also observed during docking studies with the amino acids present in the active site of Rho-kinase. Based on the above screening, three hits (NSC 2488, NSC 2888, and NSC 4231) were chosen and subjected to in vitro Rho-kinase enzyme-based assay, followed by ex vivo rat aortic vasodilatory assay. All three compounds showed good biological activity as predicted by the model and confirmed by the docking studies.

Adherence to Oral Anticancer Medications After Implementation of an Ambulatory Adherence Program at a Large Urban Academic Hospital.

PURPOSE: Oral anticancer medications (OAMs) offer convenient administration, reducing the burden of cancer treatment, but create challenges for patients and practitioners. Using data from the Quality Oncology Practice Initiative analysis, a baseline adherence rate of 30% was identified at a large public, academic hospital. To improve OAM adherence, a quality improvement initiative was conducted. METHODS: The aim was to increase OAM patient adherence by 30 percentage points. Through cause-and-effect analysis, adherence barriers were identified, leading to the development of 2 strategies: low-cost adherence tools and a pharmacist-led adherence program. Prescription refill data were collected before and after the intervention, using prescription-fill data and specialty pharmacy records. Adherence was defined as the patient having the drug available at least 80% to less than 120% of the days evaluated for 4 treatment cycles. Other indicators collected included the number of interventions, OAM-related toxicity, emergency room visits, and hospitalizations. RESULTS: OAM adherence increased from 37% to 85% (n = 20 of 54 v 44 of 52 patients; P < .0001) in 1 year. During the study, 655 interventions were documented by the pharmacist (adherence related, n = 331; treatment related, n = 324). The number of oncology-related emergency room referrals leading to hospitalization increased from 52% (n = 13 of 25) to 62% (n = 23 of 37) during the study period. CONCLUSION: A pharmacist-led adherence program, combined with low-cost adherence tools, exceeded the goal for the adherence initiative, suggesting that a multidisciplinary collaborative approach to OAM adherence can have a significant impact on outcomes.

Improving Documentation of Pain and Constipation Management Within the Cancer Center of a Large Urban Academic Hospital.

PURPOSE: Pain and constipation are common among patients with cancer and remain inadequately controlled in many. The Quality Oncology Practice Initiative assessment of pain and constipation at the Georgia Cancer Center for Excellence at Grady Health System identified documentation to be below benchmark levels. A quality improvement initiative to improve pain and constipation management was conducted. METHODS: Given the low baseline documentation rates for pain (60%) and constipation (20%), we aimed for an increase of 20 percentage points within 1 year. On the basis of cause-and-effect analysis and provider questionnaires to understand fully the causal factors, our multidisciplinary team developed a new provider note template to integrate nurse's assessment of pain and constipation into the provider's documentation. A new order panel was developed in the electronic medical record to link appropriate orders with the pain and constipation plan. RESULTS: The integration of the initial nursing assessment into the provider note template increased pain score documentation from 66.7% to 100% (P < .01), and the pain management plan improved from 65.3% to 86.4% (P = .06). Similarly, constipation assessment documentation improved from 20.4% to 100% (P < .01), and a documented constipation plan improved accordingly from 11.2% to 29.1% (P < .01). As a result of this intervention, pain control at the third clinic visit improved from 61.5% to 86.8% (P < .01). Emergency department visits related to pain and constipation decreased (16.2% to 14.9%; P = .19), and hospitalizations marginally increased (1.6% to 3.6%) during the study period (P =.28). CONCLUSION: A standardized visit template and hardwired assessment of pain and constipation exceeded the goal for improvement in documentation and positively affected outcomes.

Stability studies of rifampicin in plasma and urine of tuberculosis patients according to the European Medicines Agency Guidelines.

Aim: The macrolide antibiotic rifampicin is prescribed against several infections, like tuberculosis disease. This drug decays to rifampicin quinone. Results/methodology: The biological fluids were diluted in a micellar solution and directly injected. Using a C18 column and a mobile phase of 0.15 M SDS-6% 1-pentanol phosphate-buffered at pH 7, running at 1 ml/min, the analytes were resolved in less than 15 min. The detection was by absorbance at 337 nm. Method was validated by the guidelines of the European Medicines Agency. Decomposition of rifampicin to rifampicin quinone was also studied. Discussion/conclusion: Procedure is rapid, easy-to-handle, economic, eco-friendly and with a high sample throughput. It was successfully used to monitor rifampicin in the plasma and urine of tubercular patients.

In-Silico QSAR Modelling of Predicted Rho Kinase Inhibitors Against Cardio Vascular Diseases.

BACKGROUND: Rho-kinase is an essential downstream target of GTP-binding protein RhoA, and plays a crucial role in the calcium-sensitization pathway. Rho-kinase pathway is critically involved in phosphorylation state of myosin light chain, leading to increased contraction of smooth muscles. Inhibition of this pathway has turned out to be a promising target for several indications such as cardiovascular diseases, glaucoma and inflammatory diseases. METHODS: The present work focuses on a division-based 2D quantitative structure-activity relationship (QSAR) analysis along with a docking study to predict structural features that may be essential for the enhancement of selectivity and potency of the target compounds. Furthermore, a set of indoles and azaindoles were also projected based on the regression equation as novel developments. Molecular docking was applied for exploring the binding sites of the newly predicted set of compounds with the receptor. RESULTS: Results of the docked conformations suggested that introduction of non-bulky and substituted groups in the hinge region of ROCK-II ATP binding pocket would improve the activity by decreasing the bulkiness or length of the compounds. CONCLUSION: ADME studies were performed to ascertain the novelty and drug-like properties of the designed molecules, respectively.

Histone Deacetylase Inhibitors: A Prospect in Drug Discovery.

Cancer is a provocative issue across the globe and treatment of uncontrolled cell growth follows a deep investigation in the field of drug discovery. Therefore, there is a crucial requirement for discovering an ingenious medicinally active agent that can amend idle drug targets. Increasing pragmatic evidence implies that histone deacetylases (HDACs) are trapped during cancer progression, which increases deacetylation and triggers changes in malignancy. They provide a ground-breaking scaffold and an attainable key for investigating chemical entity pertinent to HDAC biology as a therapeutic target in the drug discovery context. Due to gene expression, an impending requirement to prudently transfer cytotoxicity to cancerous cells, HDAC inhibitors may be developed as anticancer agents. The present review focuses on the basics of HDAC enzymes, their inhibitors, and therapeutic outcomes.

In-Silico Screening of Ligand Based Pharmacophore, Database Mining and Molecular Docking on 2, 5-Diaminopyrimidines Azapurines as Potential Inhibitors of Glycogen Synthase Kinase-3ß.

BACKGROUND: Glycogen synthase kinase-3ß plays a significant role in the regulation of various pathological pathways relating to the Central Nervous System (CNS). Dysregulation of Glycogen synthase kinase 3 (GSK-3) activity gives rise to numerous neuroinflammation and neurodegenerative related disorders that affect the whole central nervous system. OBJECTIVE: By the sequential application of in-silico tools, efforts have been attempted to design the novel GSK-3ß inhibitors. METHOD: Owing to the potential role of GSK-3ß in nervous disorders, we have attempted to develop the quantitative four featured pharmacophore model comprising two Hydrogen Bond Acceptors (HBA), one Ring Aromatic (RA), and one Hydrophobe (HY), which were further affirmed by costfunction analysis, rm2 matrices, internal and external test set validation and Guner-Henry (GH) scoring analysis. Validated pharmacophoric model was used for virtual screening and out of 345 compounds, two potential virtual hits were finalized that were on the basis of fit value, estimated activity and Lipinski's violation. The chosen compounds were subjected to dock within the active site of GSK-3ß. RESULT: Four essential features, i.e., two Hydrogen Bond Acceptors (HBA), one Ring Aromatic (RA), and one Hydrophobe (HY), were subjected to build the pharmacophoric model and showed good correlation coefficient, RMSD and cost difference values of 0.91, 0.94 and 42.9 respectively and further model was validated employing cost-function analysis, rm2-matrices, internal and external test set prediction with r2 value of 0.77 and 0.84. Docked conformations showed potential interactions in between the features of the identified hits (NCI 4296, NCI 3034) and the amino acids present in the active site. CONCLUSION: In line with the overhead discussion, and through our stepwise computational approaches, we have identified novel, structurally diverse glycogen synthase kinase inhibitors.

Lip Repositioning: A Boon in Smile Enhancement.

This clinical report describes the successful use of lip repositioning technique for the reduction of excessive gingival display. The lip repositioning technique was performed with the main objective of reducing gummy smile by limiting the retraction of elevator muscles (e.g., zygomaticus minor, levator anguli, orbicularis oris, and levator labii superioris). This technique includes removing a strip of mucosa from the maxillary buccal vestibule, creating a partial-thickness flap between mucogingival junction and upper lip musculature, and suturing the lip mucosa with mucogingival junction, resulting in a narrow vestibule and restricted muscle pull, thereby reducing gingival display.

Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis.

Cytokinesis terminates mitosis, resulting in separation of the two sister cells. Septins, a conserved family of GTP-binding cytoskeletal proteins, are an absolute requirement for cytokinesis in budding yeast. We demonstrate that septin-dependence of mammalian cytokinesis differs greatly between cell types: genetic loss of the pivotal septin subunit SEPT7 in vivo reveals that septins are indispensable for cytokinesis in fibroblasts, but expendable in cells of the hematopoietic system. SEPT7-deficient mouse embryos fail to gastrulate, and septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic machinery, including hyperacetylation/stabilization of microtubules and stalled midbody abscission, leading to constitutive multinucleation. We identified the microtubule depolymerizing protein stathmin as a key molecule aiding in septin-independent cytokinesis, demonstrated that stathmin supplementation is sufficient to override cytokinesis failure in SEPT7-null fibroblasts, and that knockdown of stathmin makes proliferation of a hematopoietic cell line sensitive to the septin inhibitor forchlorfenuron. Identification of septin-independent cytokinesis in the hematopoietic system could serve as a key to identify solid tumor-specific molecular targets for inhibition of cell proliferation.

Protective effect of Pueraria tuberosa DC. embedded biscuit on cisplatin-induced nephrotoxicity in mice.

Recently, the nephroprotective property of Pueraria tuberosa DC. tuber (PT) has been reported by our group. Here, PT-embedded biscuits were prepared and tested on cisplatin-induced nephrotoxicity in Swiss albino mice. The PT powder was characterized by RAPD (random amplified polymorphic DNA) to ascertain its authenticity and PT biscuits were prepared in different concentrations (1, 2, or 4 g of PT powder). These biscuits were given as diet for a total of 10 days, but on the 7th day cisplatin injection (8 mg/kg bw, i.p.) was given. On the 10th day animals were killed to collect kidneys for assessment of antioxidant status. Blood samples were collected on both the 7th and 10th days for assessment of liver and kidney functions. In mice, PT biscuit showed significant protection against cisplatin-induced nephrotoxicity, but there was a transient rise in alanine aminotransferase and aspartate aminotransferase at the dose of 4 g PT biscuit. Therefore, it is suggested that PT biscuit might be an effective food supplement for cancer patients undergoing cisplatin-chemotherapy. However, periodical liver function monitoring is required, especially when PT is used for longer periods or at higher doses.

Tolerance induction towards cardiac allografts under costimulation blockade is impaired in CCR7-deficient animals but can be restored by adoptive transfer of syngeneic plasmacytoid dendritic cells.

Deficiency of transplant recipients for the chemokine receptor CCR7 was originally described to slightly increase the survival time of vascularized solid organ grafts, probably due to a reduced priming of alloreactive T cells. Using a model of allotolerance induction by donor-specific splenocyte transfusion (DST) in combination with anti-CD40L mAb-mediated costimulation blockade (CSB), we show here a striking failure of CCR7-deficient (CCR7(-/-) ) recipients to tolerate cardiac allografts. Furthermore, in addition to the recently described lack of Treg, CCR7(-/-) mice were found to harbor significantly reduced numbers of plasmacytoid dendritic cells (pDCs) within peripheral as well as mesenteric lymph nodes (LNs), but not the bone marrow or spleen. pDCs had previously been suggested to function as tolerogenic APC during allograft transplantation, and a single transfer of syngeneic WT pDCs, but not conventional DCs, was indeed sufficient to rescue graft survival in DST+CSB-treated CCR7(-/-) recipients in a dose-dependent manner. We therefore conclude that the nearly complete absence of pDCs within LNs of CCR7(-/-) mice prevents the successful induction of DST+CSB-mediated allotolerance, leading to the observed acute rejection of cardiac allografts under tolerizing conditions.