Elevated protein catabolism and protein malnutrition are common in patients with chronic kidney disease (CKD) and end‐stage renal disease (ESRD). The underlying etiology includes, but is not limited to, metabolic acidosis intestinal dysbiosis; systemic inflammation with activation of complements, endothelin‐1 and renin‐angiotensin‐aldosterone (RAAS) axis; anabolic hormone resistance; energy expenditure elevation; and uremic toxin accumulation. All of these derangements can further worsen kidney function, leading to poor patient outcomes. Many of these CKD‐related derangements can be prevented and substantially reversed, representing an area of great potential to improve CKD and ESRD care. This review integrates known information and recent advances in the area of protein nutrition and malnutrition in CKD and ESRD. Management recommendations are summarized. Thorough understanding the pathogenesis and etiology of protein malnutrition in CKD and ESRD patients will undoubtedly facilitate the design and development of more effective strategies to optimize protein nutrition and improve outcomes.
COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1–14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.
Drug conjugates are conjugates comprising a tumor-homing carrier tethered to a cytotoxic agent via a linker that are designed to deliver an ultra-toxic payload directly to the target cancer cells. This strategy has been successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce their toxic side effects. Drug conjugates are being developed worldwide, with the potential to revolutionize current cancer treatment strategies. Antibody-drug conjugates (ADCs) have developed rapidly, and 14 of them have received market approval since the first approval event by the Food and Drug Administration in 2000. However, there are some limitations in the use of antibodies as carriers. Other classes of drug conjugates are emerging, such as targeted drugs conjugated with peptides (peptide-drug conjugates, PDCs) and polymers (polymer-drug conjugates, PolyDCs) with the remaining constructs similar to those of ADCs. These novel drug conjugates are gaining attention because they overcome the limitations of ADCs. This review summarizes the current state and advancements in knowledge regarding the design, constructs, and clinical efficacy of different drug conjugates.
1 August 2020 in International Journal of Antimicrobial Agents
Tumor-associated macrophages (TAMs) exert integrated effects in all aspects of tumor progression, including tumor cell proliferation, angiogenesis, invasion, and metastasis. Recently, considerable preclinical and clinical trials have demonstrated that TAM-targeted therapy is an effective antitumor therapeutic approach, especially as a complementary strategy in combination with conventional chemotherapy, radiotherapy, or emerging immunotherapy. Here, we review all of the current clinical trials targeting TAMs worldwide up to May 2021 and highlight instances of the synergetic therapeutic efficacy of TAM-targeted combined therapeutic strategies. In total, 606 clinical trials were conducted, including 143 tested products. There has been explosive growth in macrophage-targeted therapy around the world during the past decade. Most trials were at early phase, and two-thirds used macrophage-targeting therapy as part of a combination approach. The most common combination is that of traditional chemotherapy with TAM-targeted therapy, followed by immune checkpoint inhibitors and targeted drugs. TAM-targeted therapeutic approaches are a newly emerging but rapidly developing area of anticancer therapy, especially as a combinatorial therapeutic approach. Further investigation of promising combination strategies will pave the way to more effective anticancer therapies.
Information on acute kidney injury (AKI) in elderly hospitalized patients is limited. This study aims to assess the incidence, risk factors and outcomes of AKI in elderly Chinese patients. The Epidemiology of AKI in Chinese Hospitalized adults (EACH) study is a multicenter, retrospective cohort study conducted in nine regional central hospitals across China. Patients aged more than 65 years were selected from the EACH study for this analysis. A novel approach with adjustment for frequency of serum creatinine was used to estimate the incidence of AKI in elderly patients. In-hospital outcomes, including mortality, renal recovery, length of stay and daily cost of elderly patients, were analyzed and compared with outcomes in younger patients. Of 144,232 adult patients in the EACH study, 42,737 (29.63 %) patients were 65 years or older, including 9773 very elderly patients (≥80 years old). The incidence of AKI was 15.44 % in patients 65–79 years old (community-acquired (CA) AKI of 3.89 % and hospital-acquired (HA) AKI of 11.55 %) and 22.22 % in the very elderly group (CA-AKI of 6.58 % and HA-AKI of 15.64 %). The mortality rate of AKI was 10.3 % in patients aged from 65 to 80 and 19.6 % in patients older than 80 years. AKI incidence, in-hospital mortality, percentage of patients requiring dialysis and percentage without renal recovery were higher in elderly patients than in younger patients. The incidence of AKI in elderly Chinese hospitalized patients is high, which becomes a substantial burden on medical care in China.