Leading report of molecular prevalence of tick borne Anaplasma marginale and Theileria ovis in yaks (Bos grunniens) from Pakistan.

Domestic yak (Bos grunniens) is an economically important feature of the mountainous region of Gilgit-Baltistan in Pakistan where agriculture is restricted and yaks play multiple roles which includes being a source of milk, meat, hides, fuel and power. However little is known about the parasitic infections in Pakistani yaks. Aim of this research was to report the prevalence and genetic diversity of protozoa parasite (Theileria ovis, 18 S rDNA gene was targeted) and an obligate bacterium (Anaplasma marginale, msp-1 gene was amplified) in the blood that was sampled from 202 yaks collected from four districts in Gilgit-Baltistan during January 2023 till January 2024. Results revealed that 6/202 (3%) yaks were of Theileria ovis while 8/202 (4%) were Anaplasma marginale infected. Positive PCR products of both parasites were confirmed by DNA sequencing and their similarity with previously available pathogen sequences was determined by BLAST analysis. Phylogenetic tree indicated that isolates of both parasites displayed genetic. Anaplasma marginale infection varied with the sampling districts and Shigar district had the highest rate of bacterial infection. Cows were significantly more prone to Theileria ovis infection than bulls. Calf and hybrid yaks were more prone to Anaplasma marginale infection. In conclusion, this is the first report that yaks residing the Gilgit-Baltistan region in Pakistan are infected with Theileria ovis and Anaplasma marginale. Similar larger scales studies are recommended in various regions of Gilgit-Baltistan to document the infection rates of these parasites to formulate strategies that will lead to the effective control of these pathogens.

A short report on the current landscape of Artificial Intelligence (AI) in vascular surgery in Pakistan.

This study focuses on the current applications, potential, and challenges to Artificial Intelligence (AI) integration in vascular surgery with specific emphasis on its relevance in Pakistan. Despite the benefits of AI in vascular surgery, there is a substantial gap in its adoption in Pakistan compared to global standards. In our context with limited resources and a scarcity of vascular surgeons, AI can serve as a promising solution. It can enhance healthcare accessibility, improve diagnostic accuracy, and alleviate the workload on vascular surgeons. However, hurdles including the absence of a comprehensive vascular surgery database, a shortage of AI experts, and potential algorithmic biases pose significant challenges to AI implementation. Despite these obstacles, the study underscores the imperative for continued research, collaborative efforts, and investments to unlock the full potential of AI and elevate vascular healthcare standards in Pakistan.

Maternal FMR1 alleles expansion in newborns during transmission: a prospective cohort study.

INTRODUCTION: The CGG repeats in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1) gene shows increased instability upon maternal transmission. Maternal FMR1 intermediate (45-54 repeats) and premutation (PM: 55-<200 repeats) alleles usually expand to full mutation (>200 repeats) alleles in offspring and consequently, cause fragile X syndrome (FXS) in them. METHODS: In a prospective cohort study, Pakistani pregnant women in prenatal care were first screened for FMR1 expanded alleles. In the follow-up, pregnancy outcomes in women carrying FMR1 expanded alleles were recorded and their newborn offspring were also screened for FXS. RESULTS: In a total of 1950 pregnant women, 89 (4.6%) were detected carriers for FMR1 expanded alleles; however, rates of detection of expanded alleles were found significantly high in women with a history of FXS. In addition, miscarriages and birth of affected newborns with FXS were significantly more common in women carrying large size PM alleles and had a history of FXS (P = 0.0494 and P = 0.0494, respectively). CONCLUSIONS: The current study provides the first evidence of screening Pakistani pregnant women for FMR1 expanded alleles in prenatal care. Moreover, the miscarriage was also detected as a clinical predictor for FXS. IMPACT: Offspring would have a higher risk of developing FXS due to maternal FMR1 alleles expansions during transmission. This is the first prospective cohort study in Pakistan for finding FMR1 allelic status of pregnant women and their newborn offspring in follow-up. The robust offspring risk for FXS estimated in this study may be valuable information for genetic counseling of women carriers for FMR1 expanded alleles. The family history and miscarriage were detected as effective indicators for FXS carrier screening in Pakistani women.

Association of Metabolic Syndrome with Stroke, Myocardial Infarction, and Other Postoperative Complications Following Carotid Endarterectomy: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Metabolic syndrome (MetS) is a constellation of hypertension, insulin resistance, obesity, and dyslipidemia and is known to increase the risk of postoperative morbidity. This study aimed to assess the impact of MetS on stroke, myocardial infarction, mortality, and other complications following carotid endarterectomy (CEA). METHODS: We analyzed data from the National Surgical Quality Improvement Program. Patients undergoing elective CEA between 2011 and 2020 were included. Patients with American Society of Anesthesiologists status 5, preoperative length of stay (LOS) > 1 day, ventilator dependence, admission from nonhome location, and ipsilateral internal carotid artery stenosis of < 50% or 100% were excluded. A composite cardiovascular outcome for postoperative stroke, myocardial infarction, and mortality was generated. Multivariable binary logistic regression analyses were used to assess the association of MetS with the composite outcome and other perioperative complications. RESULTS: We included 25,226 patients (3,613, 14.3% with MetS). MetS was associated with postoperative stroke, unplanned readmission, and prolonged LOS on bivariate analysis. On multivariable analysis, MetS was significantly associated with the composite cardiovascular outcome (1.320 [1.061-1.642]), stroke (1.387 [1.039-1.852]), unplanned readmission (1.399 [1.210-1.619]), and prolonged LOS (1.378 [1.024-1.853]). Other clinico-demographic factors associated with the cardiovascular outcome included Black race, smoking status, anemia, leukocytosis, physiologic risk factors, symptomatic disease, preoperative beta-blocker use, and operative time ≥ 150 min. CONCLUSIONS: MetS is associated with cardiovascular complications, stroke, prolonged LOS, and unplanned readmissions following CEA. Surgeons should provide optimized care to this high-risk population and strive to reduce operative durations.

Laser energy partitioning in nanosecond pulsed laser-induced air breakdown: effect of incident laser energy.

Air breakdown is generated by a 1064 nm nanosecond pulsed laser beam, and laser energy deposited in the breakdown (E d), transmitted through the plasma region (E t) and carried away by the shock wave (E s) is estimated for the incident laser energy (E i) range of 60-273 mJ. The E d is approximately 85% of E i at 60 mJ, rapidly increasing to 92% at 102 mJ. The shock wave front velocity and radius are measured as a function of E i and propagation distance. The shock wave velocity nicely follows the v∝E i0.3 trend predicted by the laser-supported detonation wave model. The Sedov-Taylor theory is used to estimate E s, which rapidly increases with E i, but E i to E s conversion linearly decreases from 83% to 48%. At lower values of E i, most of the laser energy is carried away by the shock wave, whereas the laser energy used in plasma heating or released in the form of electromagnetic and thermal radiation becomes important at higher laser energies. This implies that laser energy partitioning is highly dependent on the value of incident laser energy. These findings provide important insights into the fundamental physics of air breakdown and will be useful in a variety of applications such as laser-induced breakdown spectroscopy, laser ignition, and laser propulsion.

Diabetic Foot Ulcers: Contemporary Assessment And Management.

Diabetic foot ulcer disease is the combination of vasculopathy, neuropathy and infection. It is important to identify the main aetiology and to treat it for optimal ulcer healing so that limb amputation may be prevented. A literature review spanning five years (2018-2021) was performed to assess the current understanding of these aetiologies and management options for their treatment. Peripheral artery disease is prevalent in patients with diabetes. Before performing any amputations, whether minor or major, vascular supply in these patients needs to be evaluated and, if needed, improved. Diabetic neuropathy is a long-term complication of uncontrolled diabetes. Patients' education is very important with respect to selfcare and prevention of foot complications arising out of minor trauma in diabetic population. Better foot care and regular use of off-loading shoe wear can prevent neuropathic diabetic foot ulcers. Infection in diabetic patients is mostly polymicrobial and it can present as superficial or deep infections. Early diagnosis, use of broad-spectrum antibiotics, and aggressive debridement, when needed, is advocated to prevent foot amputation. Contemporary treatment armamentarium provides many options for treating diabetic foot ulcers. Nevertheless, one must exhaust all preventive strategies to avoid ulcers in the first place. Once an ulcer has developed, it should be managed aggressively with appropriate soft tissue and, if required, with bony procedures. The current narrative review was planned to explore the current understanding about the main aetiologies of diabetic foot ulcers and about the available treatment options.

Radio basilic transposition arteriovenous fistula : An effective but less frequently used haemodialysis vascular access - A Case Report.

Radiobasilic transposition arteriovenous fistula (RBTAVF) is often ignored as an option for haemodialysis access. We present the case of a 57-year-old male patient who presented at the AKUH vascular clinic, Karachi, for the creation of long-term haemodialysis vascular access. He had small-sized forearm cephalic vein (1.5 mm), but reasonable sized basilic vein. He underwent successful RBTAVF. Most of the guidelines recommend brachiocephalic fistula (BCF) as the second choice following radiocephalic AVF. This case recommends the inclusion of RBAVF as the second choice for vascular access in international guidelines, in addition to BCF and BBF.

Fragile X premutation carrier screening in Pakistani preconception women in primary care consultation.

PURPOSE: Women of reproductive age who carry fragile X premutation (PM) alleles have 56 to 200 CGG repeats in the 5'-untranslated region of FMR1 gene are at increased risk for producing children with intellectual disabilities (ID) or autism spectrum disorders (ASD) due to expansion of PM alleles to full mutation alleles (> 200 repeats) during maternal transmission. METHODS: In present study fragile X PM carrier screening was performed in total 808 women who were consulting primary health care centers for preconception care in Khyber Pakhtunkhwa region of Pakistan between April, 2018 and December, 2020. Polymerase chain reaction (PCR) was performed for detection of PM carrier women and the CGG repeats number was confirmed by Southern blotting and capillary electrophoresis. RESULTS: The prevalence rate for PM carriers among preconception women was found to be 0.7% that was contributed by 0.5% women in risk group (RG1) with family history of ID and 0.2% in risk group 2 (RG2) with family history of ASD. PM carrier women had at least one affected child or sibling. In addition, the preconception women with FMR1 PM alleles were found to be at increased risk for primary ovary insufficiency (RG1: P = 0.0265, RG2: P = 0.0389), postpartum depression (RG1: P = 0.0240, RG2: P = 0.0501) and neuropsychiatric disorders (RG1: P = 0.0389, RG2: P = 0.0432). CONCLUSIONS: Current study provides first evidence of fragile X PM carrier screening in Pakistani preconception women in primary care consultation. Findings of current study may help to improve preconception care and to reduce burden of fragile X associated disorders in our population.

Bmp4 Synexpression Gene, Sizzled, Transcription Is Collectively Modulated by Smad1 and Ventx1.1/Ventx2.1 in Early Xenopus Embryos.

Sizzled (Szl) is a secreted frizzled protein, having a sequence homology with the extracellular cysteine-rich domain (CRD) of the Wnt receptor, 'Frizzled'. Contrary to the other secreted frizzled like proteins (Sfrps), szl belongs to the bone morphogenetic protein 4 (Bmp4) synexpression group and is tightly coexpressed with Bmp4. What is not known is how the szl transcription achieves its Bmp4 synexpression pattern. To address the molecular details of szl transcription control, we cloned a promoter of size 1566 base pairs for szl (bps) from the Xenopus laevis genomic DNA. Luciferase and eGFP reporter gene results of this szl promoter (-1566 bp) in its activation and repression patterns by Bmp4/Smad1 and a dominant negative Bmp4 receptor (DNBR) were similar to those of the endogenous szl expression. Reporter gene assays and site-directed mutagenesis of the szl promoter mapped an active Bmp4/Smad1 response element (BRE) and a cis-acting element, which competitively share a direct binding site for Ventx1.1 and Ventx2.1 (a Ventx response element, VRE). Smad1 and ventx2.1 alone increased szl promoter activity; in addition, the binding of each protein component was enhanced with their coexpression. Interestingly, Ventx1.1 repressed this reporter gene activity; however, Ventx1.1 and Ventx2.1 together positively regulated the szl promoter activity. From our analysis, Ventx2.1 binding was enhanced by Ventx1.1, but Ventx1.1 inhibitory binding was inhibited by co-injection of Ventx2.1 for the VRE site. The inhibitory Ventx1.1 co-injection decreased Smad1 binding on the szl promoter. In a triple combination of overexpressed Smad1/Ventx1.1/Ventx2.1, the reduced binding of Smad1 from Ventx1.1 was recovered to that of the Smad1/Ventx2 combination. Collectively, this study provides evidence of Bmp4/Smad1 signaling for a primary immediate early response and its two oppositely behaving target transcription factors, Ventx1.1 and Ventx2.1, for a secondary response, as they together upregulate the szl promoter's activity to achieve szl expression in a Bmp4 synexpression manner.

Photocatalytic CO2 Reduction Using TiO2-Based Photocatalysts and TiO2 Z-Scheme Heterojunction Composites: A Review.

Photocatalytic CO2 reduction is a most promising technique to capture CO2 and reduce it to non-fossil fuel and other valuable compounds. Today, we are facing serious environmental issues due to the usage of excessive amounts of non-renewable energy resources. In this aspect, photocatalytic CO2 reduction will provide us with energy-enriched compounds and help to keep our environment clean and healthy. For this purpose, various photocatalysts have been designed to obtain selective products and improve efficiency of the system. Semiconductor materials have received great attention and have showed good performances for CO2 reduction. Titanium dioxide has been widely explored as a photocatalyst for CO2 reduction among the semiconductors due to its suitable electronic/optical properties, availability at low cost, thermal stability, low toxicity, and high photoactivity. Inspired by natural photosynthesis, the artificial Z-scheme of photocatalyst is constructed to provide an easy method to enhance efficiency of CO2 reduction. This review covers literature in this field, particularly the studies about the photocatalytic system, TiO2 Z-scheme heterojunction composites, and use of transition metals for CO2 photoreduction. Lastly, challenges and opportunities are described to open a new era in engineering and attain good performances with semiconductor materials for photocatalytic CO2 reduction.

Molecular Genomic Study of Inhibin Molecule Production through Granulosa Cell Gene Expression in Inhibin-Deficient Mice.

Inhibin is a molecule that belongs to peptide hormones and is excreted through pituitary gonadotropins stimulation action on the granulosa cells of the ovaries. However, the differential regulation of inhibin and follicle-stimulating hormone (FSH) on granulosa cell tumor growth in mice inhibin-deficient females is not yet well understood. The objective of this study was to evaluate the role of inhibin and FSH on the granulosa cells of ovarian follicles at the premature antral stage. This study stimulated immature wild-type (WT) and Inhibin-α knockout (Inha-/-) female mice with human chorionic gonadotropin (hCG) and examined hCG-induced gene expression changes in granulosa cells. Also, screening of differentially expressed genes (DEGs) was performed in the two groups under study. In addition, related modules to external traits and key gene drivers were determined through Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm. The results identified a number of 1074 and 931 DEGs and 343 overlapping DEGs (ODEGs) were shared in the two groups. Some 341 ODEGs had high relevance and consistent expression direction, with a significant correlation coefficient (r2 = 0.9145). Additionally, the gene co-expression network of selected 153 genes showed 122 nodes enriched to 21 GO biological processes (BP) and reproduction and 3 genes related to genomic pathways. By using principal component analysis (PCA), the 14 genes in the regulatory network were fixed and the cumulative proportion of fitted top three principal components was 94.64%. In conclusion, this study revealed the novelty of using ODEGs for investigating the inhibin and FSH hormone pathways that might open the way toward gene therapy for granulosa cell tumors. Also, these genes could be used as biomarkers for tracking the changes in inhibin and FSH hormone from the changes in the nutrition pattern.

Anti-neuropathic pain activity of a cationic palladium (II) dithiocarbamate by suppressing the inflammatory mediators in paclitaxel-induced neuropathic pain model.

BACKGROUND: Neuropathic pain is a chronic pain state that negatively impacts the quality of life. Currently, available therapies for the treatment of neuropathic pain often lack efficacy and tolerability. Therefore, the search for novel drugs is crucial to obtain treatments that effectively suppress neuropathic pain. OBJECTIVES: The present study was undertaken to investigate the antinociceptive properties of (1,4-bis-(diphenylphosphino) butane) palladium (II) chloride monohydrate (Compound 1) in a paclitaxel (PTX)-induced neuropathic pain model. METHODS: Initially, behavioral tests such as mechanical and cold allodynia as well as thermal and tail immersion hyperalgesia were performed to investigate the antinociceptive potential of Compound 1 (5 and 10 mg/kg, b.w). RT-PCR was performed to determine the effect of Compound 1 on the mRNA expression level of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-1ß, and IL-6. In addition, antioxidant protein, nitric oxide (NO), and malondialdehyde (MDA) levels were also determined. RESULTS: The results demonstrated that once-daily dosing of Compound 1 significantly suppressed the PTX-induced behavioral pain responses dose-dependently. The mRNA gene expressions of iNOS, COX-2, and inflammatory cytokines were markedly reduced by Compound 1. Furthermore, it enhanced the level of antioxidant enzymes and lowered the level of MDA and NO production. CONCLUSION: These findings suggest that the antinociceptive potential of Compound 1 in the PTX-induced neuropathic pain model is via suppression of oxidative stress and inflammation. Thus, Compound 1 might be a potential candidate for the therapeutic management of PTX induced neuropathic pain.

A Deep Learning Based Approach for Localization and Recognition of Pakistani Vehicle License Plates.

License plate localization is the process of finding the license plate area and drawing a bounding box around it, while recognition is the process of identifying the text within the bounding box. The current state-of-the-art license plate localization and recognition approaches require license plates of standard size, style, fonts, and colors. Unfortunately, in Pakistan, license plates are non-standard and vary in terms of the characteristics mentioned above. This paper presents a deep-learning-based approach to localize and recognize Pakistani license plates with non-uniform and non-standardized sizes, fonts, and styles. We developed a new Pakistani license plate dataset (PLPD) to train and evaluate the proposed model. We conducted extensive experiments to compare the accuracy of the proposed approach with existing techniques. The results show that the proposed method outperformed the other methods to localize and recognize non-standard license plates.

Wnt/ß-catenin Pathway-Mediated PPARδ Expression during Embryonic Development Differentiation and Disease.

The Wnt/ß-catenin signaling pathway plays a crucial role in early embryonic development. Wnt/ß-catenin signaling is a major regulator of cell proliferation and keeps embryonic stem cells (ESCs) in the pluripotent state. Dysregulation of Wnt signaling in the early developmental stages causes several hereditary diseases that lead to embryonic abnormalities. Several other signaling molecules are directly or indirectly activated in response to Wnt/ß-catenin stimulation. The crosstalk of these signaling factors either synergizes or opposes the transcriptional activation of ß-catenin/Tcf4-mediated target gene expression. Recently, the crosstalk between the peroxisome proliferator-activated receptor delta (PPARδ), which belongs to the steroid superfamily, and Wnt/ß-catenin signaling has been reported to take place during several aspects of embryonic development. However, numerous questions need to be answered regarding the function and regulation of PPARδ in coordination with the Wnt/ß-catenin pathway. Here, we have summarized the functional activation of the PPARδ in co-ordination with the Wnt/ß-catenin pathway during the regulation of several aspects of embryonic development, stem cell regulation and maintenance, as well as during the progression of several metabolic disorders.

Frequency of limb salvage after infra-inguinal bypass for chronic limb-threatening ischaemia in diabetics: A retrospective study.

A study was conducted to assess the number of limbs salvaged among diabetic patients with chronic limb-threatening ischaemia after infra-inguinal bypass surgeries at a low- to middle-income country (LMIC) hospital. It was a retrospective chart review of diabetic patients who underwent infra-inguinal bypass for lower leg revascularisation for chronic limb-threatening ischaemia at the Section of Vascular Surgery, Aga Khan University Hospital, Karachi (Pakistan) from January 2008 till April 2019. Diabetic patients with chronic limb-threatening ischaemia had a salvage rate of 90.5%(29/32) after infra-inguinal bypass surgery in our set up which is comparable to those described in the literature.

Endoleaks: Current concepts and treatments - A Narrative Review.

Endoleaks are the most common complications following endovascular aneurysm repair. Depending upon their origin, there are five types of endoleaks, types I-V, which can also be classified as direct and indirect endoleaks. Direct endoleaks (type I and III) have higher risk of aneurysm rupture due to rapid sac expansion, and require immediate correction. Indirect endoleaks ( type II, IV and V) have a relatively benign course compared to direct endoleaks. Most of them resolve with time and very few need interventions upon sac enlargement. Type V endotension is a special situation where there is sac enlargement despite no demonstrable endoleak. Proper planning and appropriate selection of stent-graft can prevent most of these endoleaks. With improvement in stent-graft technology, the incidence of endoleaks has been reduced. The current narrative review was planned to describe the pathophysiology, risk factors and treatment options for each type of endoleak.

Abdominal vascular injuries- what general/ trauma surgeons should know?

Abdominal vascular injuries are the common cause of death post-trauma. These are challenging injuries to manage due to severe haemodynamic instability, other associated injuries and difficulty in accessing and controlling these deep-seated vessels. Early control of bleeding can decrease mortality in these patients. Abdominal vasculature is divided into three zones, each requiring different operative strategy for exposure. Standard vascular surgery principles of achieving proximal and distal control before exploring any haematoma are followed when managing these injuries. Resuscitative endovascular balloon occlusion of aorta is a minimally invasive method of achieving proximal aortic occlusion. This also acts as bridge for definitive intervention or surgery. Endovascular interventions, including angioembolisation and stent-graft, have shown to improve outcomes, especially in patients with blunt abdominal trauma. Updated knowledge is necessary for all those directly involved in managing these patients. The current narrative review was planned to discusses relevant anatomy, principles, different surgical approaches and endovascular techniques to deal with these injuries.

Post-traumatic arteriovenous fistulae of the extremities: A case series.

Post-traumatic arteriovenous fistulae (AVF) can lead to congestive heart failure and limb ischaemia. The objective of this study was to determine the presentations, interventions, and outcomes (morbidity and mortality) of the patients treated with traumatic AVF at a university hospital between January 1995 to December 2018. Nine patients (M: F 8:1) with median age of 30 [IQR 24.5] years were included in the study. They presented as 'missed injuries' with median delay of 4 [IQR 55.25] months. Most had penetrating injuries and presented with painful limb swelling, pain, and venous ulcer. Superficial femoral and popliteal were the most involved vessels. Seven (77.7%) patients had surgery, while 2 (22.2%) had endovascular interventions. Open arterial reconstruction was performed with interposition vein in 4 (44.4%) or with prosthetic grafts in 1(11.1%) patient. There was no peri-operative morbidity or 30-day mortality. All patients had smooth recovery with limb salvage rate of 100%.

Carriers Break Barriers in Drug Delivery: Endocytosis and Endosomal Escape of Gene Delivery Vectors.

Over the past decades, major efforts were undertaken to develop devices on a nanoscale level for the efficient and nontoxic delivery of molecules to tissues and cells, for the purpose of either diagnosis or treatment of disease. The application of such devices in drug delivery has proven to be beneficial for matters as diverse as drug solubility, drug targeting, controlled drug release, and transport of drugs across cellular barriers. Multiple nanotherapeutics have been approved for clinical treatment, and more products are being evaluated in preclinical and clinical trials. However, many biological barriers hinder the medical application of nanocarriers. There are two main classes of barriers that need to be overcome by drug nanocarriers: extracellular and intracellular barriers, both of which may capture and/or destroy therapeutics before they reach their target site. This Account discusses major biological barriers that are confronted by nanotherapeutics, following their systemic administration, focusing on cellular entry and endosomal escape of gene delivery vectors. The use of pH-responsive materials to overcome the endosomal barrier is addressed. Historically, cell biologists have studied the interaction between cells and pathogens in order to unveil the mechanisms of endocytosis and cell signaling. Meanwhile, it is becoming clear that cells may respond in similar ways to artificial drug delivery systems and, consequently, that knowledge on the cellular response against both pathogens and nanoparticulate systems will aid in the design of improved nanomedicine. A close collaboration between bioengineers and cell biologists will promote this development. At the same time, we have come to realize that tools that we use to study fundamental cellular processes, including metabolic inhibitors of endocytosis and overexpression/downregulation of proteins, may cause changes in cellular physiology. This calls for the implementation of refined methods to study nanocarrier-cell interactions, as is discussed in this Account. Finally, recent papers on the dynamics of cargo release from endosomes by means of live cell imaging have significantly advanced our understanding of the transfection process. They have initiated discussion (among others) on the limited number of endosomal escape events in transfection, and on the endosomal stage at which genetic cargo is most efficiently released. Advancements in imaging techniques, including super-resolution microscopy, in concert with techniques to label endogenous proteins and/or label proteins with synthetic fluorophores, will contribute to a more detailed understanding of nanocarrier-cell dynamics, which is imperative for the development of safe and efficient nanomedicine.

Flavonoids and type 2 diabetes: Evidence of efficacy in clinical and animal studies and delivery strategies to enhance their therapeutic efficacy.

Diabetes mellitus type 2 (T2DM) is a metabolic disorder develops due to the overproduction of free radicals where oxidative stress could contribute it. Possible factors are defective insulin signals, glucose oxidation, and degradation of glycated proteins as well as alteration in glutathione metabolism which induced hyperglycemia. Previous studies revealed a link between T2DM with oxidative stress, inflammation and insulin resistance which are assumed to be regulated by numerous cellular networks such as NF-κB, PI3K/Akt, MAPK, GSK3 and PPARγ. Flavonoids are ubiquitously present in the nature and classified according to their chemical structures for example, flavonols, flavones, flavan-3-ols, anthocyanidins, flavanones, and isoflavones. Flavonoids indicate poor bioavailability which could be improved by employing various nano-delivery systems against the occurrences of T2DM. These bioactive compounds exert versatile anti-diabetic activities via modulating targeted cellular signaling networks, thereby, improving glucose metabolism, α -glycosidase, and glucose transport or aldose reductase by carbohydrate metabolic pathway in pancreatic ß-cells, hepatocytes, adipocytes and skeletal myofibres. Moreover, anti-diabetic properties of flavonoids also encounter diabetic related complications. This review article has designed to shed light on the anti-diabetic potential of flavonoids, contribution of oxidative stress, evidence of efficacy in clinical, cellular and animal studies and nano-delivery approaches to enhance their therapeutic efficacy. This article might give some new insights for therapeutic intervention against T2DM in near future.