Advances in active targeting of ligand-directed polymeric nanomicelles via exploiting overexpressed cellular receptors for precise nanomedicine.

Many of the utilized drugs which already exist in the pharmaceutical sector are hydrophobic in nature. These drugs are characterized by being poorly absorbed and difficult to formulate in aqueous environments with low bioavailability, which could result in consuming high and frequent doses in order to fulfil the required therapeutic effect. As a result, there is a decisive demand to find modern alternatives to overcome all these drawbacks. Self-assembling polymeric nanomicelles (PMs) with their unique structure appear to be a fascinating choice as a pharmaceutical carrier system for improving the solubility & bioavailability of many drugs. PMs as drug carriers have many advantages including suitable size, high stability, prolonged circulation time, elevated cargo capacity and controlled therapeutic release. Otherwise, the pathological features of some diseased cells, like cancer, allow PMs with particle size <200 nm to be passively uptaken via enhanced permeability and retention phenomenon (EPR). However, the passive targeting approach was proven to be insufficient in many cases. Consequently, the therapeutic efficiency of these PMs can be further reinforced by enhancing their cellular internalization via incorporating targeting ligands. These targeting ligands can enhance the assemblage of loaded cargos in the intended tissues via receptor-mediated endocytosis through exploiting receptors robustly expressed on the exterior of the intended tissue while minimizing their toxic effects. In this review, the up-to-date approaches of harnessing active targeting ligands to exploit certain overexpressed receptors will be summarized concerning the functionalization of the exterior of PMs for ameliorating their targeting potential in the scope of nanomedicine.

Influence of thyroid autoimmunity at various clinical stages of hypothyroidism on the risk of miscarriage before 20 weeks of gestation.

PURPOSE: We aimed to clarify the influence of thyroid autoantibodies at various clinical stages of hypothyroidism on the risk of pregnancy loss before 20 weeks of gestation. METHODS: We enrolled 230 pregnant women with a history of recurrent miscarriage. Detailed clinical history, physical examination, and laboratory testing of thyroid function, antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-TG) were applied among all participants. RESULTS: Coexisting overt hypothyroidism and positive thyroid autoantibodies quadrupled the risk of miscarriage in women before 20 weeks of gestation (OR 4.04, 95% CI = 2.08-7.96, P < 0.001). Women with subclinical hypothyroidism (OR 1.44, 95% CI = 0.81-2.57, P = 0.132,) or who were euthyroid (OR 1.53, 95% CI = 0.86-2.73, P = 0.094) showed a non-significant risk of miscarriage even with positive thyroid autoantibodies. Thyroid-stimulating hormone (TSH) was positively correlated with the number of miscarriages rather than anti-TPO (P < 0.001 and 0.209, respectively). CONCLUSION: Coexistence of overt hypothyroidism and thyroid autoimmunity was the only significant driver of pregnancy loss before 20 weeks of gestation.

Influence of time factor and albuminuria on characteristics of patients with type 2 diabetes Mellitus before, during and 1 year after COVID-19 recovery.

BACKGROUND: The potential effects of time factor and albuminuria on the morbid alterations in patients with type 2 diabetes (T2D) and COVID-19 are still unclear. We aimed to address the morbid alterations and the potential effects of time factor and albuminuria on the patients' characteristics before, during, and 1 year after COVID-19 recovery. METHODS: 83 patients with T2D were included, at Mansoura University Hospital, Egypt (July 2021-December 2021). Data of detailed history, physical examination, laboratory tests were recruited from files of the patients. Diagnosis and resolution of COVID-19 were established by Real time polymerase chain reaction (RT-PCR) test of SARS-CoV2. Complete blood count (CBC), renal and hepatic function tests, multiple measures of morning spot urine albumin to creatinine ratio (urine ACR), glycosylated hemoglobin (HBA1c), lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ferritin, neutrophil to lymphocyte ratio (NLR), vitamin D3, intact parathyroid hormone (intact PTH), serum calcium were applied to all participants. RESULTS: Our participants had a mean age of 45 years, 60.2% male, 56.6% were hospitalized, and 25.3% were admitted to ICU for severe COVID-19. Albuminuria was prevalent in 71.1% before, 98.8% during, and 92.8% after COVID-19 recovery. Patients with albuminuria showed older age, longer duration of T2D, more frequent severe COVID-19 and hospitalization (p = 0.03, p < 0.001, p = 0.023& p = 0.025) respectively. Body mass index (BMI), mean arterial blood pressure, ESR, CRP, ferritin, NLR, HBA1c, triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio, vitamin D3, serum calcium, alkaline phosphatase (ALP), hepatic aminotransferases, and urine ACR showed significant alterations throughout the study (p < 0.001 for all). Although the interaction between time and albuminuria showed non-significant effect on all studied parameters, we noticed relevant main effects of time factor on Body mass index (BMI), HBA1c, glomerular filtration rate (eGFR), TG/HDL ratio, NLR, vitamin D3, (p < 0.001 for all). Moreover, albuminuria showed main effects on BMI, serum creatinine, and intact PTH (p = 0.019, 0.005 & <0.001), respectively. CONCLUSION: The characteristics of patients with T2D significantly altered throughout the study. Time factor and albuminuria exerted relevant main effects on the patients' characteristics without significant effect of their interaction.

Influence of sodium-glucose Co-transporter 2 inhibitors on clinical and biochemical markers of dehydration during the Holy Ramadan.

BACKGROUND AND AIMS: Alteration of the hydration status with the use of sodium-glucose co-transporter- 2 inhibitors (SGLT2i) during the Holy Ramadan has not been studied in depth. Precisely, we aimed to detect the potential alteration of hydration status in adult Muslims with type 2 diabetes mellitus (T2D) who used SGLT2i during Ramadan. METHODS: An observational non-interventional study included 245 patients with type 2 diabetes mellitus of matched age and sex. The study included 3 groups: empagliflozin group; 87 patients, dapagliflozin group; 85 patients and control group; 73 patients without the use of SGLT2i. Participants in each group were well-settled on their medications for more than 3 months before the onset of Ramadan. Clinical and biochemical parameters of hydration status were evaluated during the last week of Ramadan. RESULTS: We noticed a higher prevalence of orthostatic dizziness and postural hypotension among SGLT2i users than non-SGLT2i users (p < 0.001). The mean arterial blood pressure was significantly lowered among users of empagliflozin and dapagliflozin than non-SGLT2i users; 93.7 ± 5.1 and 93.1 ± 6.9 versus 106.2 ± 4.3, p < 0.001, respectively. Moreover, patients who used empagliflozin or dapagliflozin exhibited significantly higher values of urine specific gravity; 1029.6 ± 1.5 and 1029.1 ± 1.6 versus 1016.9 ± 4.4, p < 0.001, serum osmolality; 300.7 ± 10.2 and 297.8 ± 8.9 versus 290.9 ± 6.7, p < 0.001, and BUN/creatinine ratio; 24.1 ± 4.1 and 23.2 ± 4.6 versus 16.3 ± 4.2, p < 0.001 than non-SGLT2i users. CONCLUSION: Significant clinical and biochemical markers of dehydration were noticed among users of SGLT2i during the Holy Ramadan.

Long-term clinical and biochemical residue after COVID-19 recovery.

BACKGROUND: The long-term health consequences of coronavirus disease 2019 (COVID-19) are still unclear. The majority of previous trials addressed the post-COVID-19 symptoms through comprehensive medical questionnaires for relatively short periods after recovery. We tried to detect the potential pathological clinical signs and biochemical residue which persist for more than 3 months after the negative real-time polymerase chain reaction (RT-PCR) test of SARS-CoV-2. RESULTS: Among 120 COVID-19 survivors of mean age 38.29 and 55.6% male proportion, systolic blood pressure was significantly elevated ( P =0.001). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer showed higher values in COVID-19 survivors ( P < 0.001). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl trans-peptidase (GGT), and alkaline phosphatase (ALP) were significantly elevated in contrast to serum albumin that was reduced in COVID-19 survivors ( P ≤0.001). Serum lipase, amylase and albuminuria were higher in COVID-19 survivors ( P ≤0.001). Regression analysis (AOR, 95% CI) showed that ESR ( P = 0.014), haemoglobin concentration ( P = 0.039), serum lipase ( P = 0.018), blood urea nitrogen ( P = 0.003), albuminuria ( P = 0.046), 25(OH) vitamin D ( P = 0.002), and serum uric acid ( P = 0.005) were the significant predictors of COVID-19 survivors (94.8% an overall prediction). CONCLUSION: COVID-19 survivors experienced residual significant clinical and biochemical alterations that necessitate comprehensive medical care and close follow-up for longer periods.

Identification of the Molecular Basis of Nanocurcumin-Induced Telocyte Preservation within the Colon of Ulcerative Colitis Rat Model.

BACKGROUND: Telocytes (TCs) are a distinct type of interstitial cells that play a vital role in the pathogenesis of ulcerative colitis and colonic tissue hemostasis. The aim of this study was to examine the effect of nanocurcumin (NC) on the morphometric and immunohistochemical characterization of TCs in the ulcerative colitis (UC) rat model. METHODS: Forty rats were randomly divided into control, NC, UC, and UC+NC groups. At the end of the experiment, the colon was dissected and prepared for histopathological and immunohistochemical assessment. Tissue homogenates were prepared for real-time PCR assessment of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß) gene expression. Our results revealed extensive mucosal damage with inflammatory cell infiltration, significant reduction of CD34, and vimentin immunostained TCs in the colon of the UC group with significant elevation of expression of IL-6, TNF-α, and TGF-ß. The UC+NC-treated group revealed significant elevation of TC count compared to the UC group besides, a significant reduction of the three gene expression. CONCLUSION: NC successfully targeted the colonic tissue, improved the mucosal lesion, preserve TCs distribution, and count through its anti-inflammatory and fibrinolytic properties.