Unusual Dzyaloshinskii-Moriya Interaction in Graphene/Fe3GeTe2 Van der Waals Heterostructure.

Dzyaloshinskii-Moriya interaction (DMI) is shown to induce a topologically protected chiral spin texture in magnetic/nonmagnetic heterostructures. In the context of van der Waals spintronic devices, graphene emerges as an excellent candidate material. However, due to its negligible spin-orbit interaction, inducing DMI to stabilize topological spins when coupled to 3d-ferromagnets remains challenging. Here, it is demonstrated that, despite these challenges, a sizeable Rashba-type spin splitting followed by significant DMI is induced in graphene/Fe3GeTe2. This is made possible due to an interfacial electric field driven by charge asymmetry together with the broken inversion symmetry of the heterostructure. These findings reveal that the enhanced DMI energy parameter, resulting from a large effective electron mass in Fe3GeTe2, remarkably contributes to stabilizing non-collinear spins below the Curie temperature, overcoming the magnetic anisotropy energy. These results are supported by the topological Hall effect, which coexists with the non-trivial breakdown of Fermi liquid behavior, confirming the interplay between spins and non-trivial topology. This work paves the way toward the design and control of interface-driven skyrmion-based devices.

Different Critical Exponents on Two Sides of a Transition: Observation of Crossover from Ising to Heisenberg Exchange in Skyrmion Host Cu_{2}OSeO_{3}.

We present experimental investigation on critical phenomena in Cu_{2}OSeO_{3} by analyzing the critical behavior of magnetization using a new method. This is necessary as a crossover from 3D Ising to 3D Heisenberg has been observed in Cu_{2}OSeO_{3}. The proposed method is applicable to explore the physics for a wide range of materials showing trivial or nontrivial critical behavior on two sides of the transition. A magnetic phase diagram has been constructed from the critical analysis. Multiple critical points due to multiple phases and transition between them have been observed in the phase diagram of Cu_{2}OSeO_{3}.

Engineered liposomes bearing camptothecin analogue for tumour targeting: in vitro and ex-vivo studies.

Topotecan (TPT) is a semi-synthetic, water-soluble derivative of camptothecin, which inhibits the action of topoisomerase I in the S-phase of the cell cycle leading to cell death. For the effective delivery of TPT to cancer cells, pH-sensitive sialic acid modified liposomes were developed. These liposomes were prepared by the thin-film hydration method using the active loading technique. Vesicle size, polydispersity index (PDI), zeta potential, and percentage entrapment efficiency were determined to be 167 ± 3.78 nm, 0.243, -8.39 mV, and 79.88 ± 1.67%, respectively. The pH-sensitive sialic acid (SA) conjugated liposomes enhanced the drug release at acidic pH 4 (92.33 ± 4.21%) as compared to physiological pH 7.4 (63.11 ± 4.51%). A Sulforhodamine B (SRB) cytotoxicity assay was performed in Murine sarcoma S180 cell lines and the GI50 value of free TPT, Lipo, P-Lipo, SA-P-Lipo, and Adriamycin (ADR) were determined to be 10.07 ± 0.15, 27.33 ± 1.01, 28.76 ± 0.87, 15.7 ± 0.45, and 11.5 ± 0.21 µg/mL, respectively. Results obtained from the apoptosis study revealed that cell death by a combination of early apoptosis and apoptosis caused by SA-P-Lipo was ∼24 fold higher than the control. These results demonstrated that pH-sensitive sialic acid conjugated liposomes will be a potential formulation for improving the antitumor efficacy of TPT. However, further research is necessitated to expedite its applicability in clinical regimen in order to ascertain its safety and efficacy.

Mucoadhesive gastroretentive microparticulate system for programmed delivery of famotidine and clarithromycin.

AIM: The present research was aimed to develop thiolated polyacrylic acid (TPA) based microspheres (MSPs) containing famotidine (FX) and clarithromycin (CLX). METHODS: TPA was synthesised from polyacrylic acid and l-cysteine in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC). The prepared TPA was characterised using FT-IR (Fourier transform-infra red), 1H-NMR (proton nuclear magnetic resonance) spectroscopy, P-XRD (powder X ray diffraction) method, and zeta potential. The analytical tools have supported the formation of TPA. The thiolated microspheres were prepared by emulsion solvent evaporation method using 0.75% w/v polymer concentration and stirring at 400 rpm for 8 hr. RESULTS: The average particle size and zeta potential of optimised formulation was found to be 25.2 ± 1.87 µm and -26.68 mV, respectively. The entrapment efficiency of the optimised formulation was obtained 67.20% for FX and 70.20% for CLX. The developed microspheres were swelled only in 4 h from 0.5 to 0.9. The in vitro mucoadhesive study and in vitro drug release studies demonstrated that microspheres showed mucoadhesive property. In in vitro drug release studies, the release of FX and CLX were observed to be 58.68% and 60.48%, respectively from microspheres in 8 h. The thiolated microspheres showed higher adhesion time (7.0 ± 0.8 h) in comparison to the plain microspheres (2.6 ± 0.4 h). CONCLUSION: The prepared TPA based mucoadhesive microspheres can be utilised as carriers for the treatment of peptic ulcer caused by Helicobacter pylori which will offer enhanced residence time for the rational drug combination in the gastric region.

Promising Antifungal Potential of Engineered Non-ionic Surfactant-Based Vesicles: In Vitro and In Vivo Studies.

Fungal keratitis (FK) is a corneal infection caused by different fungal species. It is treated by the topical application of natamycin (NAT). Nevertheless, this approach faces many limitations like toxic effects, frequent dosing, resistance, and patient discomfort. The present research reports the development of trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes by a modified thin-film hydration method. TMC was synthesized using a one-step carbodiimide method and characterized by 1H-NMR and degree of quaternization (53.74 ± 1.06%). NAT, cholesterol (CHOL), span 60 (Sp60), and dicetyl phosphate (DCP) were used to prepare niosomes which were incubated with TMC to obtain mucoadhesive cationic NAT loaded niosomes (MCNNs). MCNNs showed a spherical shape with 1031.12 ± 14.18 nm size (PDI below 0.3) and 80.23 ± 5.28% entrapment efficiency. In vitro drug release studies showed gradual drug release from TMC coated niosomes as compared to the uncoated niosomes. MIC assay and disk diffusion assay revealed promising in vitro antifungal potential of MCNNs similar to the marketed formulation. For investigating in vivo performance, ocular retention and pharmacokinetics, ocular irritation, and ulcer healing studies were performed using the rabbit model. Mucoadhesive property and prolonged local drug release improved the safety and efficacy of NAT, suggesting that the developed niosomes could be an emerging system for effective treatment of fungal keratitis.

Exendin-4-based imaging in endogenous hyperinsulinemic hypoglycaemia cohort: A tertiary Endocrine centre experience.

CONTEXT: Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results. OBJECTIVE: To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities. DESIGN: Retrospective cross-sectional study. PATIENTS: We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n = 11), Munchausen syndrome (MS) (n = 2) and inconclusive (n = 1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma. MAIN OUTCOME MEASURES: True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization. RESULTS: In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS. CONCLUSION: 68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.

Folate Conjugated Double Liposomes Bearing Prednisolone and Methotrexate for Targeting Rheumatoid Arthritis.

PURPOSE: This investigation was aimed to explore the targeting potential of folate conjugated double liposomes (fDLs) bearing combination of synergistic drugs (Prednisolone and Methotrexate) for effective management of the rheumatoid arthritis (RA). METHODS: To overcome the drawbacks of monotherapy, a combination of prednisolone (PRD) (an anti-inflammatory agent) and methotrexate (MTX) (a disease modifying anti-rheumatoid agent, DMARDs) was chosen for dual targeting approach. fDLs were prepared in two steps i.e. development of inner liposomes (ILs) using thin film casting method followed by encapsulation of ILs within folate conjugated outer liposomes (double liposomes; fDLs). Developed liposomes were characterized for various physicochemical parameters and in vivo performance. RESULTS: fDLs were prepared using FA-PEG-4000-NH-DSPE conjugate. These double liposomes were having 429.3 ± 3.6 nm in size with 0.109 PDI, 8.01 ± 0.3 mV zeta potential (ζ) and 66.7 ± 3.9% and 45.3 ± 1.7% entrapments of PRD and MTX, respectively. After 24 h, the concentrations of PRD in blood were observed to be 8.66 ± 3.11 (ILs) and 15.13 ± 0.81% (DLs) while concentration of MTX were found to be 10.89 ± 0.69 and 2.34 ± 3.15% when given as ILs and fDLs, respectively. The concentration of both drugs in inflamed joint was observed to be higher than that in the non-inflamed joints. CONCLUSIONS: The folate conjugated double liposomes possess superior targeting efficiency than conjugated and unconjugated single liposomes.

Eudragit S100 coated microsponges for Colon targeting of prednisolone.

CONTEXT: Microsponge is a novel approach for targeting the drug to the colon for the management of colon ailments such as inflammatory bowel disease. OBJECTIVE: Prednisolone loaded microsponges (PLMs) were prepared and coated with Eudragit S 100 (ES) and evaluated for colon-specific drug delivery. MATERIALS AND METHODS: PLMs were prepared using quasi emulsion solvent diffusion technique using ethyl cellulose, triethylcitrate (1% v/v, plasticizer) and polyvinyl alcohol (Mol. Wt. 72 kDa, emulsifying agent). The developed microsponges were compressed into tablets via direct compression technique using sodium carboxymethyl cellulose (Na CMC) and magnesium stearate as super-disintegrant and lubricant, respectively. The tablets were then coated with ES to provide protection against harsh gastric environment and manifest colon-specific drug release. RESULTS: PLMs were found to be nano-porous spherical microstructures with size around 35 µm and 86% drug encapsulation efficiency. Finally, they were compressed into tablets which were coated with Eudragit S 100 In vitro drug release from ES coated tablets was carried out at various simulated gastrointestinal fluids i.e. 1 hr in SGF (pH 1.2), 2 to 3 h in SIF (pH 4.6), 4-5 h in SIF (pH 6.8), and 6-24 h in SCF (pH 7.4) and the results showed the biphasic release pattern indicating prolonged release for about 24 h. DISCUSSION AND CONCLUSION: In vitro drug release studies revealed that drug starts releasing after 5 h by the time PLMs may enter into the proximal colon. Hence maximum amount of drug could be released in the colon that may result in reduction in dose and dose frequency as well as side effects of drug as observed with the conventional dosage form of prednisolone.

Effectiveness of the health and wellness centers in improving identification and primary care of non-communicable diseases in Chhattisgarh State of India.

Introduction: India launched a national initiative named Health and Wellness Centres (HWCs) in 2018 to provide population-based primary care including for the non-communicable diseases (NCDs) in rural areas. The current study assesses whether operationalization of HWCs improved the detection of NCDs and increased the share of public sector facilities in providing NCD services. Methods: Two rounds of household surveys were conducted in rural Chhattisgarh in 2019 and 2022. With a focus on NCDs, the household survey covered a representative sample of individuals above the age of 30 years - 2760 individuals in 2019 and 2638 in 2022. Multi-variate regression analysis was carried out to determine effects of HWCs on identification of NCDs and utilization of public sector services. Results: The population covered by HWCs had 25% greater chance of being identified with NCDs as compared to the population without HWCs (AOR = 1.25, P = 0.03). The NCD patients living in areas covered by HWCs had 70% greater chance of utilizing the public healthcare facilities (AOR = 1.70, P = 0.01). In the population covered by HWCs, the share of the public sector in NCD care increased from 41.2% in 2019 to 62.1% in 2022, whereas the share of informal private providers dropped from 23.5% in 2019 to 8.4% in 2022. Conclusion: The HWCs showed effectiveness in increasing detection of NCDs at the population level and bringing a larger share of NCD patients to utilize public sector services. They can prove to be a crucial architectural correction for improving primary care service delivery for NCDs and other population health needs in India.

Clinico-epidemiological characteristics of the biliary samples and their antibiotic susceptibility pattern at a teaching hospital in Northern India.

Introduction: Bile is deemed a sterile fluid, with the presence of clinical conditions like cholelithiasis, cholecystitis, previous biliary interventions, biliary strictures, and so on, leading to bile stasis, and increases the chances of bacteriobilia. In this study, we recognize the bacterial spectrum of microorganisms isolated from bile samples, diagnostic parameters, and antibiotic sensitivity patterns. Methods: A retrospective observational study was carried out by compiling data from the hospital information system of a tertiary care center from 2021 to 2022 to evaluate biliary infections in patients who underwent surgical procedures related to the biliary tract and associated organs. Results: A total of 234 patients' bile samples were included in our study. The mean age of patients was 48.04 ± 14.74 years, with more patients below the age of 65 years among those with infected bile samples. One hundred and sixty-three (163/234, 69.66%) patients infected by 209 pathogenic microorganisms were recognized. The most common microorganism isolated was Escherichia coli (83/209, 39.71%), followed by Pseudomonas aeruginosa (37/209, 17.7%). Acinetobacter baumannii and Klebsiella pneumoniae isolate owed to more than 90% penicillin, extended-spectrum beta-lactamase, carbapenem, and fluoroquinolone resistance among all isolates. Length of hospital stay, malignant obstruction, and chronic kidney disease were identified as statistically significant risk factors that lead to the isolation of multi-drug-resistant isolates from bile culture. Conclusion: We recognized the spectrum of pathogens causing biliary tract infections at our center along with the antibiotic resistance pattern to guide and facilitate prompt and appropriate treatment by primary health care professionals and family medicine practitioners.

Integrating an algorithmic and health systems thinking approach to improve the uptake of government antenatal nutrition services in Vidisha, Madhya Pradesh (India), 2018 to 2021.

In 2018, the Government of Madhya Pradesh initiated the feasibility testing of integrating an algorithmic approach (assess, give, counsel, treat) to strengthen antenatal nutrition services in routine government-funded programmes coupled with a health system thinking approach to strengthen the health service delivery platform. Implementation phases included (1) an evidence review and stakeholder consultations (April 2018) and (2) a health systems strengthening preparedness phase (May-December 2018), including pilot testing in Vidisha district (January-December 2019) covering ∼54 100 pregnant women with 237 antenatal contact points through 241 government auxiliary nurse midwives/staff nurses. During 2020-21, feasibility testing was expanded to an additional 7 districts. We used programme registers of the Auxiliary Nurse Midwives Registers (2019-21) and National Family Health Survey data for 2016 and 2021 to show changes in the Vidisha district and 7 expansion districts. We compare the performance of Vidisha district with Ashok Nagar district, where no such intervention occurred. Comparing 2016 and 2021 data, the Vidisha district showed improvements in receipt of antenatal care in the first trimester (29 to 85%) and in four antenatal visits (17 to 54%). Using the difference-in-difference approach, a 42% net increase in first-trimester antenatal check-ups in Vidisha as compared to Ashok Nagar is observed. There was also an improvement in the maternal nutrition budget of the state from USD 8.5 million to USD 17.8 million during this period. The Vidisha initiative offers several lessons in time-effective workflow to deliver all constituents of nutrition services at various antenatal contact points through and via routine government health systems. Continued execution of the algorithm for screening, with longitudinal data on the management of all nutrition risks, will be critical to show its long-term impact on maternal morbidities and birth outcomes.

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.

Opportunities in combinational chemo-immunotherapy for breast cancer using nanotechnology: an emerging landscape.

INTRODUCTION: Breast carcinoma (BC) is one of the most frequent causes of cancer-related death among women, which is due to the poor response to conventional therapy. There are several complications associated with monotherapy for cancer, such as cytotoxicity to normal cells, multidrug resistance (MDR), side effects, and limited applications. To overcome these challenges, a combination of chemotherapy and immunotherapy (monoclonal antibodies, anticancer vaccines, checkpoint inhibitors, and cytokines) has been introduced. Drug delivery systems (DDSs) based on nanotechnology have more applications in BC treatment owing to their controlled and targeted drug release with lower toxicity and reduced adverse drug effects. Several nanocarriers, such as liposomes, nanoparticles, dendrimers, and micelles, have been used for the effective delivery of drugs. AREAS COVERED: This article presents opportunities and challenges in BC treatment, the rationale for cancer immunotherapy, and several combinational approaches with their applications for BC treatment. EXPERT OPINION: Nanotechnology can be used for the early prognosis and cure of BC. Several novel and targeted DDSs have been developed to enhance the efficacy of anticancer drugs. This article aims to understand new strategies for the treatment of BC and the appropriate design of nanocarriers used as a combinational DDS.

Emerging potential of niosomes in ocular delivery.

INTRODUCTION: Niosomes have recently grabbed attention as one of the best tools for various site-specific drug delivery systems, including ophthalmic drug delivery. Surfactants (nonionic; tweens and spans) of different HLB values and cholesterol are the fundamental components for these formulations. It is an alternative controlled ocular drug delivery system to liposomes to overcome the problems associated with sterilization, large-scale production, and stability. It also enhances the adhesion or retention ability of drug at the ocular site. Hydrophilic or lipophilic or amphoteric drugs can be easily encapsulated in niosomes. Besides, niosomes are a leading vesicular system compatible with most of the drugs for site-specific delivery. AREAS COVERED: This article reveals challenges and barriers for ocular drug delivery, various transporters and receptors present in the ocular region for the transportation of therapeutics as well as nutrients, and various method of preparations, loading methods and application potential of niosomes in ocular drug delivery. EXPERT OPINION: Niosomes, a vesicular system offers numerous advantages and applicability because of its good stability, non-immunogenicity, permeation potential, and controlled release ability etc. This drug delivery system has been efficiently used in the treatment of many ocular diseases.

Curcumin Based Drug Delivery Systems for Cancer Therapy.

Cancer accounts for the second major cause of death globally. Conventional cancer therapies lead to systemic toxicity that forbids their long term application. Besides, tumor resistance and recurrence have been observed in the majority of cases. Thus, the development of such therapy, which will pose minimum side effects, is the need of the hour. Curcumin or diferuloylmethane (CUR) is a natural polyphenol bioactive (obtained from Curcuma longa) which possesses anti-cancer and chemo-preventive activity. It acts by modulating various components of signaling cascades that are involved in cancer cell proliferation, invasion, and apoptosis process. It interacts with the adaptive and innate immune systems of our body and causes tumor regression. This may be the reason behind the attainment of in vivo anti-tumor activity at a very low concentration. Its ease of availability, safety profile, low cost, and multifaceted role in cancer prevention and treatment has made it a promising agent for chemoprevention of many cancers. Regardless of the phenomenal properties, its clinical utility is haltered due to its low aqueous solubility, poor bioavailability, rapid metabolism, and low cellular uptake. In the last few years, a variety of novel drug carriers have been fabricated to enhance the bioavailability and pharmacokinetic profile of CUR to attain better targeting of cancer. In this review, the recent developments in the arena of nanoformulations, like liposomes, polymeric NPs, solid lipid NPs (SNPs), polymeric micelles, nanoemulsions, microspheres, nanogels, etc. in anticancer therapy have been discussed along with a brief overview of the molecular targets for CUR in cancer therapy and role of CUR in cancer immunotherapy.

Combination Cancer Therapy Using Multifunctional Liposomes.

Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the development of drug resistance and severe side effects. Nanodrug delivery systems (NDDSs) such as nanoparticles and liposomes are being investigated to enhance the safety and efficacy of anticancer agents. NDDS-based delivery of a single agent is not found to be effective in long-term anticancer therapy. Codelivery of more than one anticancer agent using liposomes shows great potential since it exhibits simultaneous synergistic therapeutic manifestations at the tumor site and enhances therapeutic efficacy in terms of the low-dose requirement of each agent and diminished side effects. Liposomes are lipid vesicles arranged in concentric bilayers with an aqueous core; they are versatile nanocarriers that accommodate the diverse nature of anticancer drugs (both hydrophobic and hydrophilic) at the same time. They offer a number of advantages for combinatorial drug delivery in terms of increased blood circulation, selective accumulation at tumor tissues, and stimuli responsiveness. Various combination of drugs such as paclitaxel (PTX) and topotecan, sunitinib and irinotecan, and combretastin A-4 and doxorubicin have been reported for cancer chemotherapy using liposomes. This review focuses on recent scenarios of combinatorial drug delivery using liposomes for better chemotherapeutic outcomes. This assemblage can be of great importance to researchers looking for advances in novel drug delivery approaches for better cancer treatment.

Basics to advances in nanotherapy of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer existing across the globe. It begins with the formation of polyps leading to the development of metastasis, especially in advanced stage patients, who necessitate intensive chemotherapy that usually results in a poor response and high morbidity owing to multidrug resistance and severe untoward effects to the non-cancerous cells. Advancements in the targeted drug delivery permit the targeting of tumor cells without affecting the non-tumor cells. Various nanocarriers such as liposomes, polymeric nanoparticles, carbon nanotubes, micelles, and nanogels, etc. are being developed and explored for effective delivery of cytotoxic drugs to the target site thereby enhancing the drug distribution and bioavailability, simultaneously subduing the side effects. Moreover, immunotherapy for CRC is being explored for last few decades. Few clinical trials have even potentially benefited patients suffering from CRC, still immunotherapy persists merely an experimental alternative. Assessment of the ongoing and completed trials is to be warranted for effective treatment of CRC. Scientists are paying efforts to develop novel carrier systems that may enhance the targeting potential of low therapeutic index chemo- and immune-therapeutics. Several preclinical studies have revealed the superior efficacy of nanotherapy in CRC as compared to conventional approaches. Clinical trials are being recruited to ascertain the safety and efficacy of CRC therapies. The present review discourses in a nutshell the molecular interventions including the genetics, signaling pathways involved in CRC, and advances in various strategies explored for the treatment of CRC with a special emphasis on nanocarriers based drug targeting.

Homozygous p.Val89Leu plays an important pathogenic role in 5α-reductase type 2 deficiency patients with homozygous p.Arg246Gln in SRD5A2.

OBJECTIVE: To evaluate the pathogenic role of a few benign variants and hypomorphic pathogenic variants in SRD5A2. DESIGN AND METHODS: We retrospectively analyzed phenotypes and genotypes in 23 Indian patients with genetically proven steroid 5α-reductase 2 (SRD5A2) deficiency. The interactions of the SRD5A2 enzymes resulting due to the most common benign variant (p.Val89Leu), the most common (hypomorphic) pathogenic variant (p.Arg246Gln) and the double variants (p.Val89Leu and p.Arg246Gln) in SRD5A2 were compared with that of the wild type (WT) enzyme by molecular dynamics (MD) simulation. RESULTS: The majority (n = 19, 82.61%) of patients presented for atypical genitalia and had male gender identity (16/20). Including the two novel ones (p.Leu83Pro, p.Ala28Leufs*103), a total of nine different pathogenic variants were observed. p.Arg246Gln was the most common pathogenic variant (n = 12). Homozygous p.Arg246Gln (n = 9) variant was associated with milder undervirilization (Sinnecker score of ≤3a: 8/9 vs 6/14, P = 0.04) and had concurrent homozygous p.Val89Leu in all patients. Interestingly, asymptomatic fathers of two index patients were homozygous for p.Arg246Gln which questioned the pathogenicity of the variation as a sole factor. Unlike all symptomatic homozygous p.Arg246Gln patients who were also homozygous for p.Val89Leu, asymptomatic homozygous p.Arg246Gln fathers were heterozygous for p.Val89Leu. On MD simulation SRD5A2 p.Val89Leu-Testeosterone (T) and SRD5A2 p.Arg246Gln-T complexes, but not SRD5A2 p.Val89Leu and p.Arg246Gln-T complex, demonstrated close interaction between NADPH and T as that of SRD5A2 WT-T. CONCLUSIONS: p.Arg246Gln may not be pathogenic as a sole variation even in the homozygous state; additional contribution of homozygous p.Val89Leu variant may be essential for the pathogenicity of p.Arg246Gln in SRD5A2.

Evaluation of Antiarthritic Effect of Culinary-Medicinal Oyster Mushroom Pleurotus ostreatus cv. Florida (Agaricomycetes) on Complete Freund's Adjuvant Induced Arthritis in Rats.

The present study evaluates the antiarthritic effect of hydroethanolic extract of Pleurotus ostreatus cv. Florida, which was tested against adjuvant induced arthritis in rat models. Arthritis was induced by administration of complete Freund's adjuvant into the subplantar surface of left paw of rats. The extract was given orally at doses 200 mg/ kg and 400 mg/kg and piroxicam was administered intraperitonially (4 mg/kg). In vitro testing on parameters including antiproteinestrase, albumin denaturation and heat induce hemolysis was also carried out. There was significant decrease (p < 0.001) in proteinase activity and membrane stabilization in vivo studies on cv. Florida extract treated rats showed a significant (p < 0.001) decrease in paw volume, joint diameter, and spontaneous change in body weight recorded for 21 days. The treatment also resulted in an increase in rats' gripping activity compared with arthritic control rats. X-ray examinations showed a decrease in joint swelling. Histopathological examination of the extract treated group showed a significant decrease in joint space. There was also an increase in antibody levels. The antioxidant parameters showed a significant (p < 0.001) increase in superoxide dismutase and catalase enzymatic activities. Thus P. ostreatus cv. Florida extract demonstrates a potent antioxidant activity in a rat model. It is concluded that the P. ostreatus cv. Florida extract contains medicinally important constituents that show antiarthritic activity in rats.

Novel Strategies for Targeting Prostate Cancer.

Prostate cancer (PCa) is a worldwide issue, with a rapid increase in its occurrence and mortality. Over the years, various strategies have been implemented to overcome the hurdles that exist in the treatment of PCa. Consistently, there is a change in opinion about the methodologies in clinical trial that have engrossed towards the treatment of PCa. Currently, there is a need to resolve these newly recognized challenges by developing newer rational targeting systems. The ongoing clinical protocol for the therapy using different targeting systems is undertaken followed by local targeting to cancer site. A number of new drug targeting systems like liposomes, nanoemulsions, magnetic nanoparticles (MNPs), solid lipid nanoparticles, drug-peptide conjugate systems, drug-antibody conjugate systems, epigenetic and gene therapy approaches, and therapeutic aptamers are being developed to suit this protocol. Recent advancements in the treatment of PCa with various nanocarriers have been reported with respect to newly identified biological barriers and intended to solve the contexts. This review encompasses the input of nanotechnology in particular targeting of PCa which might escape the lifethreatening side effects and potentially contribute to bring fruitful clinical outcomes.