Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes.

When compared to the challenges associated with traditional dosage forms, medication delivery systems based on nanotechnology have been a huge boon. One such candidate for medication delivery is spanlastics, an elastic nanovesicle that can transport a diverse array of medicinal compounds. The use of spanlastics has been associated with an increase in interest in alternative administration methods. The non-ionic surfactant or surfactant blend is the main component of spanlastics. The purpose of this review was primarily to examine the potential of spanlastics as a delivery system for a variety of medication classes administered via diverse routes. Science Direct, Google Scholar, and Pubmed were utilized to search the academic literature for this review. Several studies have demonstrated that spanlastics greatly improve therapeutic effectiveness, increase medication absorption, and decrease drug toxicity. This paper provides a summary of the composition and structure of spanlastics along with their utility in the delivery of various therapeutic agents by adopting different routes. Additionally, it provides an overview of the numerous disorders that may be treated using drugs that are contained in spanlastic vesicles.

Ambient pressure synthesis and structure and magnetic properties of a new A- and B-site ordered multinary quadruple perovskite.

Quadruple perovskites with high magnetic transition temperatures are an interesting class of compounds but are synthesized typically under high pressure. Ambient pressure synthesis of new multinary quadruple perovskites having a high global instability index (GII) and transition temperature can be interesting for future exploration of high-TC oxides. A new A- and B-site ordered multinary quadruple perovskite, LaCu3Fe2RuSbO12, is synthesized by conventional solid-state reactions at ambient pressure. Rietveld structure refinement revealed that the compound crystallizes in the Pn3̄ space group with a lattice parameter of 7.4556(4) Å. The compound showed complete 1 : 3 ordering of La and Cu at the A-site and 1 : 1 rock-salt ordering of Fe with Ru/Sb at the B-site. The compound is also probed with scanning and transmission electron microscopy and XPS to investigate the chemical composition, microstructure, lattice and oxidation states of the elements. Magnetic studies revealed antiferromagnetic (AFM) correlations with magnetic ordering transitions at ∼170 and 40 K. Furthermore, the M-H hysteretic behavior at 100 and 5 K indicated ferrimagnetism due to short-range AFM interactions among Fe3+(3d5) and Ru4+(4d4) spins involving Cu2+(↑)-Fe3+(↓)-Ru4+(↑) triads. The specific heat data reaffirmed the magnetic signatures while electrical transport showed semiconducting behavior with variable range hopping. The details of synthesis and structural and compositional studies along with the magnetic and electrical transport properties of LaCu3Fe2RuSbO12 are reported in this paper.

Implementation of the recommended immunohistochemistry algorithm for classification of peripheral T-cell lymphoma, not otherwise specified into the prognostically significant GATA3 and TBX21 subtypes.

INTRODUCTION: Current molecular research has shown the several oncogenic pathways that give rise to the peripheral T-cell lymphoma, not otherwise defined (PTCL, NOS) subtypes, which alter prognosis and might have predictive value. This study was conducted to assess the immunohistochemistry (IHC) algorithm by Amador et al for the subtyping of PTCL, NOS and determine its applicability in relation to the clinicopathological profile. METHODS: This study included 43 patients with PTCL, NOS diagnosis. Following the use of IHC for the transcription factors GATA3, TBX21, CCR4, and CXCR3, two pathologists subtyped the samples. Comprehensive clinicopathological correlation was carried out. RESULTS: Applying the algorithm of Amador et al., cases were classified into GATA3 (20), TBX21 (15), and unclassified (8) subtypes. No significant association with clinical parameters of subtypes or CD4/ CD8 positivity was observed. Although a higher proportion of cases in the TBX21 subgroup showed a polymorphic population compared with the GATA3 subgroup, which had a monomorphic population, no significant p-value (0.111) was observed. Two Lennert lymphomas were classified into the GATA3 subgroup. Multivariate analysis showed no significant difference in overall survival (p-value = 0.105) and progression-free survival (p-value = 0.0509) between IHC-defined subtypes; trends indicate that overall survival and progression-free survival are worse in the GATA3 subgroup. CONCLUSION: Although the algorithm is reproducible, a proportion of cases remains unclassifiable and may require additional investigation and gene expression profiling. The GATA3 subgroup was found to have a monomorphic population with a poor overall prognosis and thus requires a larger sample size for validation.

A Tertiary Center Case Series on Postpartum Rectus Sheath Hematoma: An Unveiled Identity.

Rectus sheath hematoma is a well-recognized, uncommon clinical entity and may not be the initial consideration when evaluating a postpartum patient with abdominal pain or mass. Here, we report three cases of postpartum rectus sheath hematomas (RSH) managed during the last three years. The mean age of the patient was 28 (25-30) years. All patients had a history of cesarean section and presented with pain and distension in the abdomen. The cesarean was performed eight days, one day, and three days in cases 1, 2, and 3, respectively, before presentation to the hospital. Two (Cases 1 and 3) of the three patients received conservative care and were discharged in stable condition. One patient (Case 2) who was operated on for RSH and hemoperitoneum expired due to multiorgan dysfunction syndrome (MODS). Our case series suggests that, depending on the severity of the hematoma and the hemodynamic condition of the patient, RSHs may require medical intervention ranging from conservative management to surgical treatment. Early diagnosis and intervention help prevent hazardous complications and prevent maternal morbidity and mortality.

Phylogenomic evaluation of Mangrovimicrobium sediminis gen. nov. sp. nov., the first nitrogen fixing member of the family Halieaceae adapted to mangrove habitat and reclassification of Halioglobus pacificus to Pseudohaliglobus pacificus comb. nov.

The taxonomic position and genomic characteristics of a nitrogen fixing and polymer degrading marine bacterium, strain SAOS 164 isolated from a mangrove sediment sample was investigated. Sequence analysis based on 16S rRNA gene identified it as a member of family Halieaceae with closest similarity to Haliea salexigens DSM 19537T (96.3 %), H. alexandrii LZ-16-2T (96.2 %) and Parahaliea maris HSLHS9T (96.0 %) but was distantly related to the genera Haliea, Parahaliea and Halioglobus in phylogenetic trees. In order to ascertain the exact taxonomic position, phylogeny based on RpoBC proteins, whole genome, core and orthologous genes, and comparative analysis of metabolic potential retrieved the strain in an independent lineage clustering along with the genera Halioglobus, Pseudohalioglobus and Seongchinamella. Further, various genome based delimitation parameters represented by mol % GC content, percentage of conserved proteins (POCP), and amino acid identity (AAI) along with chemotaxonomic markers (i.e. fatty acids and polar lipids) supported the inferences of genome based phylogeny and indicated that the strain SAOS 164 belongs to a novel genus. The genome was mapped to 4.8 Mb in size with 65.1 % DNA mol% G + C content. In-silico genomic investigation and phenotyping revealed diverse metabolite genes/pathways related to polymer hydrolysis, nitrogen fixation, light induced growth, carbohydrate, sulfur, phosphorus and amino acid metabolism, virulence factors, defense mechanism, and stress-responsive elements facilitating survival in the mangrove habitat. Based on polyphasic taxonomic approach including genome analyses, a novel genus Mangrovimicrobium sediminis gen. nov. sp. nov. (=SAOS 164T = MTCC 12907T = KCTC 52755T = JCM 32136T) is proposed. Additionally, the reclassification of Halioglobus pacificus (=DSM 27932T = KCTC 23430T = S1-72T) to Pseudhalioglobus pacificus comb. nov. is also proposed.

Quality of life and symptom burden in hematological cancer patients receiving hematopoietic stem cell transplantation: an observational study at Regional Cancer Centre, India.

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT. METHODS: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation. RESULTS: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2. CONCLUSION: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time.

Urinary extracellular vesicles-encapsulated miRNA signatures: A new paradigm for urinary bladder cancer diagnosis and classification.

Bladder cancer (BCa) stands as prevalent malignancy of the urinary system globally, especially among men. The clinical classification of BCa into non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) is crucial for prognosis and treatment decisions. However, challenges persist in current diagnostic methods like Urine cytopathology that shows poor sensitivity therefore compromising on accurately diagnosing and monitoring BCa. In recent years, research has emphasized the importance of identifying urine and blood-based specific biomarkers for BCa that can enable early and precise diagnosis, effective tumor classification, and monitoring. The convenient proximity of urine with the urinary bladder epithelium makes urine a good source of noninvasive biomarkers, in particular urinary EVs because of the packaged existence of tumor-associated molecules. Therefore, the review assesses the potential of urinary extracellular vesicles (uEVs) as noninvasive biomarkers for BCa. We have elaborately reviewed and discussed the research that delves into the role of urinary EVs in the context of BCa diagnosis and classification. Extensive research has been dedicated to investigating differential microRNA (miRNA) expressions, with the goal of establishing distinct, noninvasive biomarkers for BCa. The identification of such biomarkers has the potential to revolutionize early detection, risk stratification, therapeutic interventions, and ultimately, the long-term prognosis of BCa patients. Despite notable advancements, inconsistencies persist in the biomarkers identified, methodologies employed, and study populations. This review meticulously compiles reported miRNA biomarkers, critically assessing the variability and discrepancies observed in existing research. By synthesizing these findings, the article aims to direct future studies toward a more cohesive and dependable approach in BCa biomarker identification, fostering progress in patient care and management.

Transdermal Drug Delivery Systems: A Focused Review of the Physical Methods of Permeation Enhancement.

The skin is the body's largest organ and serves as a site of administration for various medications. Transdermal drug delivery systems have several advantages over traditional delivery systems. It has both local and systemic therapeutic properties. Controlled plasma drug levels, reduced dosing frequency, and avoidance of hepatic first-pass metabolism are just a few of these systems' advantages. To achieve maximum efficacy, it is critical to understand the kinetics, physiochemical properties of the drug moiety, and drug transport route. This manuscript focused on the principles of various physical means to facilitate transdermal drug delivery. Some examples are iontophoresis, electrophoresis, photomechanical waves, ultrasound, needleless injections, and microneedles. Mechanical, chemical, magnetic, and electrical energy are all used in physical methods. A major advantage of physical methods is their capability to abbreviate pain, which can be used for effective disease management. Further investigation should be carried out at the clinical level to understand these methods for effective drug delivery.

Effect of CYP2C19 polymorphism on response to bortezomib-based therapy in multiple myeloma patients.

BACKGROUND: Bortezomib, a commonly used anti-myeloma drug, is metabolized by liver microsomal enzymes which may be polymorphic and responsible for lack of response in 30% patients. Hence, the association of CYP2C19 polymorphism with treatment response was explored in this study. METHODS: Treatment naive multiple myeloma (MM) patients, eligible for bortezomib-based induction treatment, were recruited as per the inclusion - exclusion criteria. The genotyping of CYP2C19 was done using polymerase chain reaction-restriction fragment length polymorphism for *2, *3 and *17 alleles. The incidence and severity of peripheral neuropathy were noted at follow-up visits and graded as per CTCAE criteria ver 5.0. RESULTS: Total 220 patients were recruited from August 2016 till May 2021; with a mean age of 55.6 (9.5) years and 65.9% males. Bortezomib+cyclophosphamide+dexamethasone (41.8%) and bortezomib+lenalidomide+dexamethasone (38.2%) were the most prescribed regimens. The CYP2C19 was polymorphic in 38.6%, 2.3% and 23.7% patients for *2, *3 and *17 allele respectively. There were 195 treatment responders and 25 non-responders, and CYP2C19*2 allele was different between responders and non-responders (p = 0.02). All extensive metabolisers (n = 54) were noted to be treatment responders. Peripheral neuropathy was reported by 23.2% patients. The frequency of peripheral neuropathy was somewhat lower in patients having either *2/*2 or *3/*3 allele pattern for CYP2C19 (p = 0.44). CONCLUSIONS: Polymorphism in CYP2C19 enzyme is likely to have an impact on bortezomib treatment response and peripheral neuropathy. The study suggests the role of pharmacogenetics in personalised treatment of MM.

Borderline tumours of ovary and fertility preservation-Outcomes from a tertiary care center in India.

OBJECTIVE: Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. METHODS: A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. RESULTS: Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. CONCLUSION: FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database.

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Cost-Effectiveness of Novel Agent Regimens for Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients in India.

BACKGROUND: Survival outcomes for multiple myeloma have improved dramatically since the introduction of novel therapeutic agents. While these drugs are highly effective in improving survival outcomes and quality of life in patients with multiple myeloma, they come at a significant cost. We assessed the cost-effectiveness of bortezomib-based triplet or quadruplet drug regimens in isolation and followed by autologous hematopoietic stem cell transplantation (AHSCT) for the treatment of newly diagnosed multiple myeloma (NDMM) in the Indian context. METHODS: A Markov model was developed to assess the health and economic outcomes of novel drug regimens with and without AHSCT for the treatment of NDMM in India. We estimated the lifetime quality-adjusted life-years (QALYs) and costs in each scenario. The incremental cost-effectiveness ratios (ICERs) were computed and compared against the current willingness-to-pay threshold of a one-time per capita gross domestic product of ₹146,890 (US$1,927.70) for India. Parameter uncertainty was assessed through Monte Carlo probabilistic sensitivity analysis. RESULTS: Among seven treatment sequences, the VCd (bortezomib, cyclophosphamide, dexamethasone) alone arm has the lowest cost and health benefits as compared to four treatment sequences, namely VTd (bortezomib, thalidomide, dexamethasone) alone, VRd (bortezomib, lenalidomide, dexamethasone) alone, VRd plus AHSCT and DVRd (Daratumumab, bortezomib, lenalidomide, dexamethasone) plus AHSCT. It was found that VTd plus AHSCT and VCd plus AHSCT arms were extendedly dominated (ED) by combination of two alternative treatments. Among the five non-dominated strategies, VRd has a lowest incremental cost of ₹ 2,20,093 (US$2,888) per QALY gained compared to VTd alone followed by VRd plus AHSCT [₹3,14,530 (US$4,128) per QALY gained] in comparison to VRd alone. None of the novel treatment sequences were found to be cost-effective at the current WTP threshold of ₹1,46,890 (US$1,927.7). CONCLUSION: At the current WTP threshold of one-time per capita GDP (₹ 146,890) of India, VRd alone and VRd plus AHSCT has 38.1% and 6.9% probability to be cost-effective, respectively. Reduction in current reimbursement rates of novel drugs, namely VRd, lenalidomide, and pomalidomide plus dexamethasone under national insurance program and societal cost of transplant by 50%, would make VRd plus AHSCT and VTd plus AHSCT cost-effective at an incremental cost of ₹40,671 (US$34) and ₹97,639 (US$1,281) per QALY gained, respectively.

Enhanced tissue distribution of ritonavir-loaded nanostructured lipid carriers-recommending its dose reduction.

Human immunodeficiency virus (HIV) mainly attacks lymphocytes of the human immune system. The untreated infection leads to acquired immune deficiency syndrome (AIDS). Ritonavir (RTV) belongs to protease inhibitors (PIs), the crucial contributors of the combination therapy used in the treatment of HIV that is called highly active antiretroviral therapy (HAART). Formulations targeting the lymphatic system (LS) play a key role in delivering and maintaining therapeutic drug concentrations in HIV reservoirs. In our previous study, we developed RTV-loaded nanostructured lipid carriers (NLCs), which contain the natural antioxidant alpha-tocopherol (AT). In the current study, the cytotoxicity of the formulation was studied in HepG2, MEK293, and H9C2 cell lines. The formulation efficacy to reach the LS was evaluated through a cycloheximide-injected chylomicron flow blockade model in Wistar rats. Biodistribution and toxicity studies were conducted in rodents to understand drug distribution patterns in various organs and to establish the safety profile of the optimized formulation (RTV-NLCs). From the MTT assay, it was found that the cell viability of the formulation is comparable with the pure drug (RTV-API). More than 2.5-folds difference in AUC was observed in animals treated with RTV-NLCs with and without cycloheximide injection. Biodistribution studies revealed higher drug exposure in the lymphoidal organs with the RTV-NLCs. No significant increase in serum biomarkers for hepatotoxicity was observed in rats dosed with the RTV-NLCs. The current study reveals the lymphatic uptake of the RTV-NLCs and their safety in rodents. As the tissue distribution of RTV-NLCs is high, hence re-adjusting the RTV-NLCs dose to get the response equivalent to RTV-API may be more beneficial with respect to its safety and efficacy.

Elucidating the Role of miRNA-326 Modulating Hedgehog Signaling in Pancreatic Carcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies worldwide characterized by poor prognosis. MicroRNAs (miRNAs) function as the key regulators in carcinogenesis and may act as noninvasive biomarkers in various malignancies including PDAC. The present study aimed to elucidate the role of miR-326, a known modulator of hedgehog (Hh) pathway in PDAC. MATERIALS AND METHODS: miR-326 circulating levels were assessed in 105 PDAC patients, 31 with chronic pancreatitis (CP) and 36 healthy controls by quantitative Polymerase chain reaction. The expression of miR-326 and smoothened (SMO) was checked in surgical PDAC tissue. SMO protein expression was analyzed by immunohistochemistry in different groups. Finally, the role of miR-326 as a modulator of Hh pathway was assessed in vitro. RESULTS: Our results demonstrate that miR-326 is downregulated in both blood and tissue of PDAC patients as compared with controls. In contrast, the target gene/protein expression of SMO is upregulated in PDAC. Moreover, the tumor stromal expression of SMO was found to be clinically associated with lymph-node metastasis and vascular encasement in PDAC. Overexpression of miR-326 in Panc1 cell line was found to induce downregulation of SMO suggesting the tumor suppressor role of miR-326 in PDAC. CONCLUSIONS: Taken together, miR-326 acts as a tumor suppressor in PDAC by modulating Hh pathway. It may be a promising target for the development of efficient drug therapies for the treatment of PDAC.

Daratumumab in Indian patients with relapsed and refractory multiple myeloma: a prospective, multicenter, phase IV study.

Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients. Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.

Biologic Antiresorptive: Denosumab.

Background: Osteoporosis is an age-related common bone disorder characterized by low bone mineral density and increased fragility fracture risk. Various Antiresorptive medications are being used to target osteoclast mediated bone resorption to prevent bone loss and reduce fracture risk. About Denosumab: Denosumab is a novel biological antiresorptive drug that belongs to the class of monoclonal antibodies. It binds to and inhibits the cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), which is requisite for osteoclast differentiation, function and survival. Effectiveness: Denosumab has been shown to be a potent and effective therapy for osteoporosis, with clinical trial data demonstrating significant improvement in bone mineral density (BMD) and reductions in fracture risk at various skeletal sites for more than 10 years of treatment. Safety Profile: Denosumab has a favourable benefit/risk profile, with low rates of complications such as infection, atypical femoral fracture and osteonecrosis of the jawbone. Challenges: However, denosumab treatment requires continuous administration, as discontinuation leads to rapid bone mineral loss and increased risk of multiple vertebral fractures due to rebound of bone turnover. Therefore, modification to another anti-osteoporosis drug therapy after denosumab discontinuation is required to maintain bone health. Conclusion: Denosumab is a promising biological antiresorptive therapy for osteoporosis that offers high efficacy and safety, but also poses challenges for long-term management.

Combination Therapy of Denosumab and Teriparatide in Osteoporosis.

Osteoporosis is a chronic disease that often requires long-term treatment for many years. The clinician should know about all the drugs that are currently being used for treatment in osteoporosis and their mechanism of action, efficacy, safety profile, mode of administration and number of years they can be given safely without causing significant adverse effects. The categories of drugs that are currently being used for osteoporosis are antiresorptives such as oral and intravenous bisphosphonates, denosumab, and anabolics like teriparatide. This article will focus on the combination therapy of denosumab and teriparatide and will discuss how this combination is better than other class of drugs when given alone or in combination in osteoporosis patients especially those who are at high risk of fragility fractures.

Enhancing temozolomide antiglioma response by inhibiting O6-methylguanine-DNA methyltransferase with selected phytochemicals: in silico and in vitro approach.

The aim of our study was to investigate the potential of rutin, catechin, dehydrozingerone, naringenin, and quercetin, both alone and in combination with temozolomide, to inhibit the expression of O6-methylguanine-DNA methyltransferase (MGMT) in glioma cells. MGMT has been shown to be a major cause of temozolomide resistance in glioma. Our study used both in silico and in vitro methods to assess the inhibitory activity of these phytochemicals on MGMT, with the goal of identifying the most effective combination of compounds for reducing temozolomide resistance. After conducting an initial in silico screening of natural compounds against MGMT protein, five phytochemicals were chosen based on their high docking scores and favorable binding energies. From the molecular docking and simulation studies, we found that quercetin showed a good inhibitory effect of MGMT with its high binding affinity. C6 glioma cells showed increased cytotoxicity when treated with the temozolomide and quercetin combination. It was understood from the isobologram and combination index plot that the drug combination showed a synergistic effect at the lowest dose. Quercetin when combined with temozolomide significantly decreased the MGMT levels in C6 cells in comparison with the other drugs as estimated by ELISA. The percentage of apoptotic cells increased significantly in the temozolomide-quercetin group indicating the potency of quercetin in decreasing the resistance of temozolomide as confirmed by acridine orange/ethidium bromide staining. Our experiment hence suggests that temozolomide resistance can be reduced by combining the drug with quercetin which will serve as an effective therapeutic target for glioblastoma treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03821-7.

Metronomic chemotherapy in ovarian cancer.

Translational research and the development of targeted therapies have transformed the therapeutic landscape in epithelial ovarian cancer over the last decade. However, recurrent ovarian cancer continues to pose formidable challenges to therapeutic interventions, necessitating innovative strategies to optimize treatment outcomes. Current research focuses on the development of pharmaceuticals that target potential resistance pathways to DNA repair pathways. However, the cost and toxicity of some of these therapies are prohibitive and majority of patients lack access to clinical trials. Metronomic chemotherapy, characterized by the continuous administration of low doses of chemotherapeutic agents without long treatment breaks, has emerged as a promising approach with potential implications beyond recurrent setting. It acts primarily by inhibition of angiogenesis and activation of host immune system. We here review the mechanism of action of metronomic chemotherapy, as well as its current role, limitations, and avenues for further research in the management of epithelial ovarian cancer.