CRISPR/Cas9-based genome editing and functional analysis of SlHyPRP1 and SlDEA1 genes of Solanum lycopersicum L. in imparting genetic tolerance to multiple stress factors.

CRISPR/Cas is a breakthrough genome editing system because of its precision, target specificity, and efficiency. As a speed breeding system, it is more robust than the conventional breeding and biotechnological approaches for qualitative and quantitative trait improvement. Tomato (Solanum lycopersicum L.) is an economically important crop, but its yield and productivity have been severely impacted due to different abiotic and biotic stresses. The recently identified SlHyPRP1 and SlDEA1 are two potential negative regulatory genes in response to different abiotic (drought and salinity) and biotic stress (bacterial leaf spot and bacterial wilt) conditions in S. lycopersicum L. The present study aimed to evaluate the drought, salinity, bacterial leaf spot, and bacterial wilt tolerance response in S. lycopersicum L. crop through CRISPR/Cas9 genome editing of SlHyPRP1 and SlDEA1 and their functional analysis. The transient single- and dual-gene SlHyPRP1 and SlDEA1 CRISPR-edited plants were phenotypically better responsive to multiple stress factors taken under the study. The CRISPR-edited SlHyPRP1 and SlDEA1 plants showed a higher level of chlorophyll and proline content compared to wild-type (WT) plants under abiotic stress conditions. Reactive oxygen species accumulation and the cell death count per total area of leaves and roots under biotic stress were less in CRISPR-edited SlHyPRP1 and SlDEA1 plants compared to WT plants. The study reveals that the combined loss-of-function of SlHyPRP1 along with SlDEA1 is essential for imparting significant multi-stress tolerance (drought, salinity, bacterial leaf spot, and bacterial wilt) in S. lycopersicum L. The main feature of the study is the detailed genetic characterization of SlDEA1, a poorly studied 8CM family gene in multi-stress tolerance, through the CRISPR/Cas9 gene editing system. The study revealed the key negative regulatory role of SlDEA1 that function together as an anchor gene with SlHyPRP1 in imparting multi-stress tolerance in S. lycopersicum L. It was interesting that the present study also showed that transient CRISPR/Cas9 editing events of SlHyPRP1 and SlDEA1 genes were successfully replicated in stably generated parent-genome-edited line (GEd0) and genome-edited first-generation lines (GEd1) of S. lycopersicum L. With these upshots, the study's key findings demonstrate outstanding value in developing sustainable multi-stress tolerance in S. lycopersicum L. and other crops to cope with climate change.

Pyrazolo - Pyrimidines as Targeted Anticancer Scaffolds - A Comprehensive Review.

BACKGROUND: Globally, cancer is the leading cause of death, which causes 10 million deaths yearly. Clinically, several drugs are used in treatment but due to drug resistance and multidrug resistance, there occurs a failure in the cancer treatment. OBJECTIVES: The present review article is a comprehensive review of pyrazole and pyrimidine hybrids as potential anticancer agents. METHOD: The review comprises more than 60 research works done in this field. The efficiency of the reported pyrazolopyrimidine fused heterocyclic with their biological data and the influence of the structural aspects of the molecule have been discussed. RESULT: This review highlighted pyrazolo-pyrimidines as targeted anticancer agents with effect on multiple targets. CONCLUSION: The review will be helpful for the researchers involved in targeted drugs for cancer therapy for designing new scaffolds with pyrazolo-pyrimidine moieties.

Ayurvedic management central serous retinopathy - A case report.

BACKGROUND: Central Serous Retinopathy (CSR) is an eye disease that causes visual impairment ascribable to fluid accumulation in the retina's macular area. CSR leads to the blurring of vision associated with metamorphopsia. The cause of the disease is unknown. The practitioners of contemporary science offer treatment only after observing for 3-4 months to resolve the fluid. The blurring of vision may persist even after oedema has resolved. If oedema does not resolve, they undertake laser photodynamic therapy or photocoagulation, which results in permanent damage to neuroretina and impaired visual acuity. According to Ayurveda, symptoms of blurred vision and metamorphopsia indicate Vata Dusti in eyes. CASE & INTERVENTION: A 53-year-old man, who sought Ayurvedic treatment for the blurring of vision in the last ten days, was diagnosed with CSR in the right eye. He underwent one course of Ayurvedic management, comprised of oral medication, including Punarnvadi kashaya, Candraprabha Vati, and Tiktaka ghrita, external treatments like Shiropichu (application of medicated oil on the bregma) and Kriyakalpa (eye treatment) like Anjana karma. OUTCOMES: At the end of a month of the Ayurvedic treatment, visual acuity in the right eye improved to 6/6, and Optic Coherence Tomography affirmed complete resolution of CSR (OCT). A one year follow up confirmed the non-recurrence of the disease. CONCLUSION: Ayurvedic treatment effectively resolves oedema within a short time with a marked visual outcome. Patients of CSR would benefit from the same if treated promptly in the early stage itself. Such patients shall be encouraged to opt for Ayurveda as a primary treatment modality.

Correction: Engineered nanostructures within sol-gel bioactive glass for enhanced bioactivity and modulated drug delivery.

Correction for 'Engineered nanostructures within sol-gel bioactive glass for enhanced bioactivity and modulated drug delivery' by Lakshmi M. Mukundan et al., J. Mater. Chem. B, 2022, https://doi.org/10.1039/d2tb01692c.

Engineered nanostructures within sol-gel bioactive glass for enhanced bioactivity and modulated drug delivery.

The engineering of nanocrystalline phase in amorphous oxide materials such as bioactive glass is emerging as a new area of great technological and scientific interest in the field of biomaterials. This study reports for the first time the infusion of apatite nanocrystals in sol-gel-derived bioactive glass using P123 as the structure-directing agent. The synthesis of a multicomponent 80SiO2-15CaO-5P2O5 bioactive glass material having a hierarchically ordered mesoporous structure with uniformly grown nanocrystals of apatite was achieved through a sono-assisted surfactant-templated sol-gel method. The bulk crystallographic analysis together with microstructural characterizations shows that the nanocrystalline apatite domains are uniformly dispersed as well as embedded along the mesopores. These nanocrystalline domains were found to influence the textural properties. In addition, macroscopic evidence for higher signs of bonelike matrix formation was observed by the biomineralization study in simulated body fluids. Osteostimulatory effects of these glass samples were evident by cultures in a osteogenic and non-osteogenic mediums with human osteosarcoma cells and a higher osteopromotive potential was authenticated by the alkaline phosphatase activity and alizarin red staining. Further, this study shows a new strategy to prolong the drug release period on account of the nanocrystalline phase and hierarchically positioned mesopores, thus making it a better drug delivery matrix as well.

Multitarget Directed Ligand Approaches for Alzheimer's Disease: A Comprehensive Review.

BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease, and a drug which targets a single protein would not provide a cure for this disease. Currently available drugs for AD are all palliative rather than curative. FDA approved only five drugs for the treatment of AD, which include tacrine, donepezil, galantamine, rivastigmine, and memantine. Tacrine has been discontinued due to its hepatotoxicity. The lack of therapeutic effectiveness of the single-target drugs and multifactorial etiology of AD have led to the design of multitarget directed ligands for AD. OBJECTIVE: The researchers in this field are constantly making efforts to develop a drug which may prove to be the exact cure for this disease by exploring the different biological targets associated with AD. The present review comprises various multitarget approaches and tools used for finding out a lead compound or a new drug, which will provide a cure for AD. METHODS: We have scrutinized and reviewed 75 research articles published in various peer reviewed journals in the last two decades in the field of multi target directed ligand approaches for the discovery of a new therapeutic agent for AD. RESULTS: The review highlights the recent advances in the field of AD research and shows that the battle for the discovery of an effective drug for AD is in process and AD still remains an incurable disease for which treatment is just palliative. CONCLUSION: The review might be helpful for researchers working on multi target directed ligands against AD.

Sorption of As(III) and As(V) on chemically synthesized manganese dioxide.

Sorption of As(III) and As(V) on manganese dioxide was studied by batch equilibration method using (76)As radioactive tracer. Manganese dioxide was prepared by two different methods viz. reacting (a) KMnO(4) solution with MnSO(4) solution, and (b) KMnO(4) solution with concentrated hydrochloric acid. Manganese dioxide was characterized by zeta potential measurement, surface area measurement, thermogravimetry (TG), differential thermal analysis (DTA) and X-ray diffraction (XRD) techniques. Point of zero charge (PZC) for manganese dioxide was between pH 3 and 4. Radioactive tracer ((76)As) was prepared by neutron irradiation of arsenious oxide in self serve facility of CIRUS reactor followed by conversion to As(III) and As(V), by appropriate chemical methods. Sorption of As(III) and As(V) were studied separately, between pH 1 to 11, using (i) freshly prepared, (ii) air-dried and (iii) aged manganese dioxide. Sorption of As(III) and As(V) on freshly prepared as well as aged manganese dioxide, from both the methods was greater than 98% between pH 1 to 9 and decreased above pH 9. Percentage sorption was comparable for manganese dioxide prepared by both the methods in different batches. Sorption capacity was ∼2 mg g(-1) for both As(III) and As(V). Arsenic was desorbed from the manganese dioxide by 0.1 M sodium hydroxide and oxidation state of desorbed arsenic was determined by solvent extraction method. It was found that the desorbed arsenic was present in As(V) oxidation state, independent of the initial oxidation states. This simple and direct chemical evidence, establishing that As(III) is converted to As(V) by manganese dioxide, is reported for the first time. Sorption of As(III) and As(V) on manganese dioxide did not cause an increase in manganese concentration above solubility limit confirming that Mn(2+), formed during oxidation of As(III) to As(V), was re-adsorbed.