Deciphering the mechanistic role of Bacillus paramycoides (PM51) and Bacillus tequilensis (PM52) in bio-sorption and phyto-assimilation of Cadmium via Linum usitatissimum L. Seedlings.

Three Cd2+ resistant bacterium's minimal inhibition concentrations were assessed and their percentages of Cd2+ accumulation were determined by measurements using an atomic absorption spectrophotometer (AAS). The results revealed that two isolates Bacillus paramycoides (PM51) and Bacillus tequilensis (PM52), identified by 16S rDNA gene sequencing, showed a higher percentage of Cd2+ accumulation i.e., 83.78% and 81.79%, respectively. Moreover, both novel strains can tolerate Cd2+ levels up to 2000 mg/L isolated from district Chakwal. Amplification of the czcD, nifH, and acdS genes was also performed. Batch bio-sorption studies revealed that at pH 7.0, 1 g/L of biomass, and an initial 150 mg/L Cd2+ concentration were the ideal bio-sorption conditions for Bacillus paramycoides (PM51) and Bacillus tequilensis (PM52). The experimental data were fit to Langmuir isotherm measurements and Freundlich isotherm model R2 values of 0.999 for each of these strains. Bio sorption processes showed pseudo-second-order kinetics. The intra-diffusion model showed Xi values for Bacillus paramycoides (PM51) and Bacillus tequilensis (PM52) of 2.26 and 2.23, respectively. Different surface ligands, was investigated through Fourier-transformation infrared spectroscopy (FTIR). The scanning electron microscope SEM images revealed that after Cd2+ adsorption, the cells of both strains became thick, adherent, and deformed. Additionally, both enhanced Linum usitatissimum plant seed germination under varied concentrations of Cd2+ (0 mg/L, 250 mg/L,350 mg/L, and 500 mg/L). Current findings suggest that the selected strains can be used as a sustainable part of bioremediation techniques.

Folic acid modified precision nanocarriers: charting new frontiers in breast cancer management beyond conventional therapies.

Breast cancer presents a significant global health challenge, ranking highest incidence rate among all types of cancers. Functionalised nanocarriers offer a promising solution for precise drug delivery by actively targeting cancer cells through specific receptors, notably folate receptors. By overcoming the limitations of passive targeting in conventional therapies, this approach holds the potential for enhanced treatment efficacy through combination therapy. Encouraging outcomes from studies like in vitro and in vivo, underscore the promise of this innovative approach. This review explores the therapeutic potential of FA (Folic acid) functionalised nanocarriers tailored for breast cancer management, discussing various chemical modification techniques for functionalization. It examines FA-conjugated nanocarriers containing chemotherapeutics to enhance treatment efficacy and addresses the pharmacokinetic aspect of these functionalised nanocarriers. Additionally, the review integrates active targeting via folic acid with theranostics, photothermal therapy, and photodynamic therapy, offering a comprehensive management strategy. Emphasising rigorous experimental validation for practical utility, the review underscores the need to bridge laboratory research to clinical application. While these functionalised nanocarriers show promise, their credibility and applicability in real-world settings necessitate thorough validation for effective clinical use.

A neoteric annotation on the advances in combination therapy for Parkinson's disease: nanocarrier-based combination approach and future anticipation. Part II: nanocarrier design and development in focus.

INTRODUCTION: The current treatment modalities available for Parkinson's disease (PD) prove inadequate due to the inherent constraints in effectively transporting bioactive compounds across the blood-brain barrier. The utilization of synergistic combinations of multiple drugs in conjunction with advanced nanotechnology, emerges as a promising avenue for the treatment of PD, offering potential breakthroughs in treatment efficacy, targeted therapy, and personalized medicine. AREAS COVERED: This review provides a comprehensive analysis of the efficacy of multifactorial interventions for PD, simultaneously addressing the primary challenges of conventional therapies and highlighting how advanced technologies can help overcome these limitations. Part II focuses on the effectiveness of nanotechnology for improving pharmacokinetics of conventional therapies, through the synergistic use of dual or multiple therapeutic agents into a single nanoformulation. Significant emphasis is laid on the advancements toward innovative integrations, such as CRISPR/Cas9 with neuroprotective agents and stem cells, all effectively synergized with nanocarriers. EXPERT OPINION: By using drug combinations, we can leverage their combined effects to enhance treatment efficacy and mitigate side effects through lower dosages. This article is meant to give nanocarrier-mediated co-delivery of drugs and the strategic incorporation of CRISPR/Cas9, either as an independent intervention or synergized with a neuroprotective agent.

A neoteric annotation on the advances in combination therapy for Parkinson's disease: nanocarrier-based combination approach and future anticipation. Part I: exploring theoretical insights and pharmacological advances.

INTRODUCTION: Parkinson's disease (PD) is a neurological condition defined by a substantial reduction in dopamine-containing cells in the substantia nigra. Levodopa (L-Dopa) is considered the gold standard in treatment. Recent research has clearly shown that resistance to existing therapies can develop. Moreover, the involvement of multiple pathways in the nigrostriatal dopaminergic neuronal loss suggests that modifying the treatment strategy could effectively reduce this degeneration. AREAS COVERED: This review summarizes the key concerns with treating PD patients and the combinations, aimed at effectively managing PD. Part I focuses on the clinical diagnosis at every stage of the disease as well as the pharmacological treatment strategies that are applied throughout its course. It methodically elucidates the potency of multifactorial interventions in attenuating the disease trajectory, substantiating the rationale for co-administration of dual or multiple therapeutic agents. Significant emphasis is laid on evidence-based pharmacological combinations for PD management. EXPERT OPINION: By utilizing multiple drugs in a combination fashion, this approach can leverage the additive or synergistic effects of these agents, amplify the spectrum of treatment, and curtail the risk of side effects by reducing the dose of each drug, demonstrating significantly greater efficacy.

Fabrication of TPGS decorated Etravirine loaded lipidic nanocarriers as a neoteric oral bioavailability enhancer for lymphatic targeting.

Etravirine (ERVN) is a potential NNRTI (non-nucleoside reverse transcriptase inhibitor) in treating HIV infection. It possesses extremely low oral bioavailability. The present research aims to optimize the formulation and characterization of TPGS-enriched ERVN-loaded lipid-based nanocarriers (NLCs) for HIV-infected patients. The formulation, ERVN-TPGS-NLCs, was optimized by central composite rotational design using a modified-solvent emulsification process. Various characterization parameters of NLCs were evaluated, including globule size of 121.56 ± 2.174 nm, PDI of 0.172 ± 0.042, the zeta potential of - 7.32 ± 0.021 mV, %EE of 94.42 ± 8.65% of ERVN and %DL was 8.94 ± 0.759% of ERVN and spherical shape was revealed by TEM. PXRD was also performed to identify the crystallinity of the sample. In-vitro drug release showed % a cumulative drug release of 83.72 ± 8.35% at pH 1.2 and 90.61 ± 9.11% at pH 6.8, respectively, whereas the % cumulative drug release from drug suspension (ERVN-S) was found to be 21.13 ± 2.01% at pH 1.2 and 24.84 ± 2.51 at pH 6.8 at the end of 48 h. Further, the intestinal permeation study and confocal microscope showed approximately three-fold and two-fold increased permeation in ERVN-TPGS-NLCs and ERVN-NLCs across the gut sac compared to ERVN-S. Hemolysis compatibility and lipolysis studies were performed to predict the in-vivo fate of the formulation. The pharmacokinetic study revealed a 3.13-fold increment in the relative bioavailability, which agrees with the ex-vivo studies, and lymphatic uptake was validated by using cycloheximide along with designed formulation, which showed the impact of lymphatic uptake in AUC. This study ensures that ERVN-TPGS-NLCs take lymphatic uptake to minimize the first-pass metabolism followed by improved oral bioavailability of ERVN. Thus, the enhanced bioavailability of ERVN can reduce the high dose of ERVN to minimize the adverse effects related to dose-related burden.

A medical image encryption scheme based on Mobius transformation and Galois field.

Data security and privacy are considered to be the biggest problems faced by service providers who have worked with public data for a long time. A key element of modern encryption that is utilized to increase textual confusion is the Substitution box (S-box) and the algebraic strength of the S-box has a significant impact on how secure the encryption method is. In this article, we present a unique method that uses a linear fractional transformation on a finite field to produce cryptographically robust S-boxes. Firstly, we choose a specific irreducible polynomial of degree 8 in Z2[x] to construct GF(28). Later, we used the action of PGL(2,GF(28)) on GF(28) to generate a robust S-box. The effectiveness of the built-in S-box was evaluated using several criteria including non-linearity, differential uniformity, strict avalanche criteria, linear approximation probability, and bit independence criterion. The proposed S-box's characteristics are compared to those of most recent S-boxes to confirm the higher performance. Additionally, the S box was used to encrypt images to show its usefulness for multimedia security applications. We performed several tests, including contrast, correlation, homogeneity, entropy, and energy, to evaluate the success of the encryption technique. The proposed method for ciphering an image is very effective, as proven by its comparison with several S boxes.

Potential of Nanocarrier-Associated Approaches for Better Therapeutic Intervention in the Management of Glioblastoma.

Glioblastoma, commonly known as glioblastoma multiforme (GBM), is one of the deadliest and most invasive types of brain cancer. Two factors account for the majority of the treatment limitations for GBM. First, the presence of the blood-brain barrier (BBB) renders malignancy treatment ineffective, leading to recurrence without full recovery. Second, several adverse effects are associated with the drugs used in conventional GBM treatment. Recent studies have developed nanocarrier systems, such as liposomes, polymeric micelles, dendrimers, nanosuspensions, nanoemulsions, nanostructured lipid carriers, solid lipid nanocarriers, metal particles, and silica nanoparticles, which allow drug-loaded formulations to penetrate the BBB more effectively. This has opened up new possibilities for overcoming therapy issues. Extensive and methodical searches of databases such as PubMed, Science Direct, Google Scholar, and others were conducted to gather relevant literature for this work, using precise keyword combinations such as "GBM," "brain tumor," and "nanocarriers." This review provides deep insights into the administration of drugs using nanocarriers for the management of GBM and explores new advancements in nanotechnology. It also highlights how scientific developments can be explained in connection with hopeful findings about the potential of nanocarriers for the future successful management of GBM.

"Midwives are heroes of the country": qualitative evaluation of a midwifery education program in South Sudan.

Background: Countries affected by armed conflict have higher maternal mortality than stable settings. South Sudan has one of the highest maternal mortality ratios in the world, with an estimated 789 maternal deaths per 100,000 live births. Long-term socio-political instability has contributed to significant challenges in its health system. To reduce maternal and newborn morbidity and mortality, South Sudan must increase the number of skilled midwives. Methods: A cross-sectional mixed methods study was conducted in 2022 to assess the midwifery education program at three schools receiving support from International Medical Corps in South Sudan, including in-depth interviews with 15 midwifery school graduates currently working as midwives, their supervisors, 16 school faculty (in dyads), and two Ministry of Health officials; and nine focus group discussions with women clients of graduate midwives. Results: Participants identified strengths of the schools, including being well equipped with trained and competent teaching staff, competency-based curriculum, including practical training which prepared graduate midwives to apply their skills in practice. Weaknesses of the program included its dependence on donor funding, inadequate mentorship and number of tutors, and insufficient practice for some services due to low client load at clinical sites. Additionally, participants identified challenges affecting midwives' ability to provide good quality care, including lack of equipment and supplies, low client load, low salaries, and insecurity due to conflict. Nevertheless, women in the community appreciated the immense work that midwives do. Midwives were respected by the community at large, and graduates expressed pride and satisfaction in their job, as well as the positive impact they have had in providing critical services to communities. Discussion: Overall, the quality of the midwifery education program appears to be strong, however gaps in the program and the provision of quality care remain. The findings highlight the need to ensure sustained funding for midwifery education, as well as health system strengthening to ensure midwives can practice their skills. Continued investment in midwifery education and training is critical to reduce high maternal mortality and morbidity in South Sudan.

Nanotechnology revolutionises breast cancer treatment: harnessing lipid-based nanocarriers to combat cancer cells.

One of the most common cancers that occur in females is breast cancer. Despite the significant leaps and bounds that have been made in treatment of breast cancer, the disease remains one of the leading causes of death among women and a major public health challenge. The therapeutic efficacy of chemotherapeutics is hindered by chemoresistance and toxicity. Nano-based lipid drug delivery systems offer controlled drug release, nanometric size and site-specific targeting. Breast cancer treatment includes surgery, chemotherapy and radiotherapy. Despite this, no single method of treatment for the condition is currently effective due to cancer stem cell metastasis and chemo-resistance. Therefore, the employment of nanocarrier systems is necessary in order to target breast cancer stem cells. This article addresses breast cancer treatment options, including modern treatment procedures such as chemotherapy, etc. and some innovative therapeutic options highlighting the role of lipidic nanocarriers loaded with chemotherapeutic drugs such as nanoemulsion, solid-lipid nanoparticles, nanostructured lipid carriers and liposomes, and their investigations have demonstrated that they can limit cancer cell growth, reduce the risk of recurrence, as well as minimise post-chemotherapy metastasis. This article also explores FDA-approved lipid-based nanocarriers, commercially available formulations, and ligand-based formulations that are being considered for further research.

Oral delivery of nerolidol alleviates cyclophosphamide-induced renal inflammation, apoptosis, and fibrosis via modulation of NF-κB/cleaved caspase-3/TGF-ß signaling molecules.

Cyclophosphamide (CP) is one of the most extensively used antineoplastic drug, but the nephrotoxicity caused by this drug is a major limiting factor for its use. Nerolidol (NERO) is a natural bioactive compound with diverse pharmacological actions. In Vitro and in vivo study was performed using HK-2 renal cells and Swiss Albino mice. Cell lines and animals were treated with NERO 25 and 50 µM + 30 µM CP (in vitro), 200 and 400 mg/kg, p.o. NERO from day 1 to day 15 + 200 mg/kg, i.p. CP on day 17 as single intraperitoneal injection (in vivo). The makers of oxidative stress, renal-specific injury markers, inflammation, apoptosis, fibrosis, and histopathological changes were studied. The study's outcome showed a significant reduction in the level of malonaldehyde and interleukin-6 (p < 0.01), tumor necrosis factor-α, IL-1ß (p < 0.001), and an increase in the superoxide dismutase, catalase, glutathione and interleukin-10 level (p < 0.01), in the in vivo study when treated with NERO 400 and compared with CP 200. In Vitro study showed reduced expression of nuclear factor kappa light chain enhancer of activated B cells, cleaved caspase-3, kidney injury molecule-1 and transforming growth factor-ß-1 (p < 0.001), when treated with NERO 50 µM whereas NERO 25 µM only reduced the level of cleaved caspase-3 (p < 0.05) when compared with 30 µM. NERO 400 also reduced uric acid (p < 0.05), urea (p < 0.01), blood urea nitrogen, and serum creatinine levels (p < 0.001) and increased the level of blood-urea-nitrogen/creatinine ratio (p < 0.001). Additionally, the level of fibrosis-specific markers such as transforming growth factor-ß1, hyaluronic acid (p < 0.01), 4-hydroxyproline, a collagen-rich area in Masson's' trichome stain, and Smad3 expression was also significantly reduced (p < 0.001). Furthermore, the outcome of multiple renal staining showed structural reversal aberrations, reduction of the thick basement membrane, and glycogen level toward normal when treated with NERO 400. Thus, the study showed a novel mechanistic modality of NERO against cyclophosphamide-induced renal toxicity. The outcome of this study can be considered a step closer to the development of an adjuvant to mitigate cyclophosphamide-induced renal toxicity among patients treated with cyclophosphamide.

Quality by design engineered, enhanced anticancer activity of temozolomide and resveratrol coloaded NLC and brain targeting via lactoferrin conjugation in treatment of glioblastoma.

The most dangerous type of high-grade astrocytoma is glioblastoma multiforme. The objective of the work was to engineer lactoferrin conjugated temozolomide and resveratrol co-loaded NLC for the treatment of glioblastoma using intranasal delivery for brain targeting. Synergistic activity of temozolomide and resveratrol was determined using combination index method and 1:1 ratio was selected. QbD approach was used to formulate and optimize NLC, with minimum particle size, maximum transmittance and entrapment efficiency using Central Composite Rotable Design (CCRD) method. The optimized LTR-NLC had desired average particle size (209.3 nm), narrow PDI along, high percentage transmittance (>95%) and better entrapment efficiency (95.26% of TEM and 87.59% of RES). From ex-vivo permeation studies it was found that the permeation at 24 h was 77.43 %, and 88.55 % from LTR-NLC and 25.76 % and 31.10% from suspension for resveratrol and temozolomide respectively. In comparison to drug suspension, NLC had nearly 3-fold increase in drug penetration. IC50 value was also significantly better in the groups treated with LTR-NLC. Hence it can be concluded that LTR-NLC may be an effective formulation for the treatment of glioblastoma, according to the findings of this investigation.

siRNA therapeutics: insights, challenges, remedies and future prospects.

INTRODUCTION: Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder. Gene silencing is supposedly intended to target any disease-causing gene, and therefore, several attempts and investments were made to exploit siRNA gene therapy and advance it into clinical settings. Despite the remarkable beneficial prospects, the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action. AREAS COVERED: The present review provides insights into the field of siRNA therapeutics, significant in vivo hurdles that mitigate the target accessibility of siRNA, and remedies to overcome these siRNA delivery challenges. Nonetheless, the current review also highlights the on-going clinical trials and the regulatory aspects of siRNA modalities. EXPERT OPINION: The siRNAs have the potential to reach previously untreated target sites and silence the concerned gene owing to their modification as polymeric or lipidic nanoparticles, conjugates, and the application of advanced drug delivery strategies. With such mounting research attempts to improve the delivery of siRNA to target tissue, we might shortly witness revolutionary therapeutic outcomes, new approvals, and clinical implications.

Information communication and technology in sports: a meticulous review.

Introduction: Sports of all kinds even though have an alluring property of keeping their onlookers stuck to their place, the introduction of Technology, however, revolutionized it all together. Not only in legal sports but also the training and teaching methods have been reformed. The use of Information Communication and Technology (ICT) based technologies [Convolutional Neural Networks (CNN), Hawkeye, Computer vision, Artificial intelligence, etc.] has moderately increased the interactive nature of sports. Employing ICT-driven technologies have continuously been increasing performance levels due to which high effective performance levels have been achieved. In addition to offering information to the users, it also acts as a means for connecting and interacting with the remaining world. In this article, we provide a review of the studies considering the developments and impact of employing ICT technology on sports, especially cricket. The study has focussed on domain-specific developments in cricket sports: developments in the batting domain, bowling domain, and wicketkeeping as well. Methods: For the study, the analysis has been done following the PRISMA guidelines. Results: The study found that even though the researchers have done justifiable work in employing technology in sports as a whole but the domain-specific contribution in sports like cricket is not at the level as is need of the hour. In addition to the mentioned domains in the study, the research should gain speed in other domains like domain-specific Talent Identification for both genders, different age groups, diverse sports, etc. Discussion: undoubtedly, the sports domain is employing technology at a vast level but a few domains like sports talent identification especially related to the most famous games like cricket require an immediate and intense focus of the researchers. Since this domain is still carrying out a traditional coach-oriented approach. There is an acute need to revolutionize the domain by incorporating modern technologies into it.

Breast Cancer Awareness and Associated Factors among Women in Pakistan: A Cross-Sectional Descriptive Study.

OBJECTIVE: Breast cancer is a highly prevalent cancer in females worldwide, with new cases around one million every year. In Pakistan, cancer of breast is the most common carcinoma in diagnosis, with one in nine females. Due to high burden of breast cancer in Pakistan, presented work purposes to investigate knowledge and awareness of breast carcinoma, its symptoms, and risk factors among Pakistani women, which play an important part in the early diagnosis of breast cancer. METHODS: A sample of 1000 females were approached generally from universities, hospitals, public places, local markets, rural areas and other cities for on-site data collection through face-to-face interviews and online data collection through telephonic interviews in Pakistan using the Breast Cancer Awareness Measure (BCAM). By using SPSS V. 25.0, the information  provided by the individuals first changed in awareness scores and was then analyzed. RESULTS: The study displayed, that mainstream participants lacked knowledge of breast carcinoma (63.2%) and the importance of its screening tools (64.7% and 83.2% lacked knowledge of mammography and BRCA tests respectively) for early detection. Almost 45% of respondents never noticed a change in their breasts. Most participants were unaware about breast cancer development is age-related and lifetime risk. Slightly more than 50% of the participants of the study were not knowledgeable regarding modifiable risk factors of breast carcinoma. A commonly known symptom was Breast lump by 53% of the respondents. Association was determined between demographic variables and breast cancer knowledge scores. Only 37.4% of respondents were found to be knowledgeable regarding breast cancer. CONCLUSION: BCAM is a productive instrument to assess awareness of breast carcinoma in females. The study indicated awareness of breast cancer is suboptimal in the population of Pakistan. Efforts should be made by public awareness campaigns and broadcasting of information about breast cancer and health education to increase awareness of risk factors.

Neuroprotective Role of DPP-4 Inhibitor Linagliptin Against Neurodegeneration, Neuronal Insulin Resistance and Neuroinflammation Induced by Intracerebroventricular Streptozotocin in Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related, multifactorial progressive neurodegenerative disorder manifested by cognitive impairment and neuronal death in the brain areas like hippocampus, yet the precise neuropathology of AD is still unclear. Continuous failure of various clinical trial studies demands the utmost need to explore more therapeutic targets against AD. Type 2 Diabetes Mellitus and neuronal insulin resistance due to serine phosphorylation of Insulin Receptor Substrate-1 at 307 exhibits correlation with AD. Dipeptidyl Peptidase-4 inhibitors (DPP-4i) have also indicated therapeutic effects in AD by increasing the level of Glucagon-like peptide-1 in the brain after crossing Blood Brain Barrier. The present study is hypothesized to examine Linagliptin, a DPP-4i in intracerebroventricular streptozotocin induced neurodegeneration, and neuroinflammation and hippocampal insulin resistance in rat model of AD. Following infusion on 1st and 3rd day, animals were treated orally with Linagliptin (0.513 mg/kg, 3 mg/kg, and 5 mg/kg) and donepezil (5 mg/kg) as a standard for 8 weeks. Neurobehavioral, biochemical and histopathological analysis was done at the end of treatment. Dose-dependently Linagliptin significantly reversed behavioral alterations done through locomotor activity (LA) and morris water maze (MWM) test. Moreover, Linagliptin augmented hippocampal GLP-1 and Akt-ser473 level and mitigated soluble Aß (1-42), IRS-1 (s307), GSK-3ß, TNF-α, IL-1ß, IL-6, AchE and oxidative/nitrosative stress level. Histopathological analysis also exhibited neuroprotective and anti-amylodogenic effect in Hematoxylin and eosin and Congo red staining respectively. The findings of our study concludes remarkable dose-dependent therapeutic potential of Linagliptin against neuronal insulin resistance via IRS-1 and AD-related complication. Thus, demonstrates unique molecular mechanism that underlie AD.

Subtractive sequence analysis aided druggable targets mining in Burkholderia cepacia complex and finding inhibitors through bioinformatics approach.

Burkholderia cepacia complex (BCC) is a group of gram-negative bacteria composed of at least 20 different species that cause diseases in plants, animals as well as humans (cystic fibrosis and airway infection). Here, we analyzed the proteomic data of 47 BCC strains by classifying them in three groups. Phylogenetic analyses were performed followed by individual core region identification for each group. Comparative analysis of the three individual core protein fractions resulted in 1766 ortholog/proteins. Non-human homologous proteins from the core region gave 1680 proteins. Essential protein analyses reduced the target list to 37 proteins, which were further compared to a closely related out-group, Burkholderia gladioli ATCC 10,248 strain, resulting in 21 proteins. 3D structure modeling, validation, and druggability step gave six targets that were subjected to further target prioritization parameters which ultimately resulted in two BCC targets. A library of 12,000 ZINC drug-like compounds was screened, where only the top hits were selected for docking orientations. These included ZINC01405842 (against Chorismate synthase aroC) and ZINC06055530 (against Bifunctional N-acetylglucosamine-1-phosphate uridyltransferase/Glucosamine-1-phosphate acetyltransferase glmU). Finally, dynamics simulation (200 ns) was performed for each ligand-receptor complex, followed by ADMET profiling. Of these targets, details of their applicability as drug targets have not yet been elucidated experimentally, hence making our predictions novel and it is suggested that further wet-lab experimentations should be conducted to test the identified BCC targets and ZINC scaffolds to inhibit them.

Nanoparticle Mediated Gene Therapy: A Trailblazer Armament to Fight CNS Disorders.

Central nervous system (CNS) disorders account for boundless socioeconomic burdens with devastating effects among the population, especially the elderly. The major symptoms of these disorders are neurodegeneration, neuroinflammation, and cognitive dysfunction caused by inherited genetic mutations or by genetic and epigenetic changes due to injury, environmental factors, and disease-related events. Currently available clinical treatments for CNS diseases, i.e., Alzheimer's disease, Parkinson's disease, stroke, and brain tumor, have significant side effects and are largely unable to halt the clinical progression. So gene therapy displays a new paradigm in the treatment of these disorders with some modalities, varying from the suppression of endogenous genes to the expression of exogenous genes. Both viral and non-viral vectors are commonly used for gene therapy. Viral vectors are quite effective but associated with severe side effects, like immunogenicity and carcinogenicity, and poor target cell specificity. Thus, non-viral vectors, mainly nanotherapeutics like nanoparticles (NPs), turn out to be a realistic approach in gene therapy, achieving higher efficacy. NPs demonstrate a new avenue in pharmacotherapy for the delivery of drugs or genes to their selective cells or tissue, thus providing concentrated and constant drug delivery to targeted tissues, minimizing systemic toxicity and side effects. The current review will emphasize the role of NPs in mediating gene therapy for CNS disorders treatment. Moreover, the challenges and perspectives of NPs in gene therapy will be summarized.