Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg^® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as “biological missiles”, is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.

Objectives: This study aims to explore the weight loss effect and safety of semaglutide as a conventional anti-obesity drug systematically in obese or overweight patients without diabetes.Methods: The randomized controlled trials (RCTs) of semaglutide in obese or overweight patients without diabetes were retrieved from PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov from database inception until 2 May 2022. Data extraction and quality assessment of studies meeting the inclusion criteria were performed, and statistical analysis was conducted by Review Manager 5.3 and Stata 14.Results: Eight studies involving 4,567 patients were enrolled in the meta-analysis. Compared with placebo, semaglutide induced a significant body weight loss (MD: −10.09%; 95% CI: −11.84 to −8.33; p ˂ 0.00001), elicited a larger reduction in body mass index (MD: −3.71 kg/m²; 95% CI: −4.33 to −3.09; p ˂ 0.00001) and waist circumference (MD: −8.28 cm; 95% CI: −9.51 to −7.04; p ˂ 0.00001), achieved weight loss of more than 5, 10, 15, and 20% with a higher proportion of participants. Semaglutide exhibited a positive effect on blood pressure, C-reactive protein, and lipid profiles, expressed more adverse effects than placebo, mainly gastrointestinal reactions. The results were stable and reliable with dose-dependence.Conclusion: Semaglutide indicated a significant weight loss with an acceptable safety for obese or overweight patients without diabetes.

Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs incorporating MMAE as payloads. Considering the increasing global use of MMAE-based ADCs, it is imperative to provide an inclusive overview of diagnostic and management strategies for this adverse event. In this review, we examine current information and what future research directions are required to better understand and manage this type of clinical challenge.

Drug conjugates have emerged as a promising alternative delivery system designed to deliver an ultra-toxic payload directly to the target cancer cells, maximizing therapeutic efficacy while minimizing toxicity. Among these, antibody-drug conjugates (ADCs) have garnered significant attention from both academia and industry due to their great potential for cancer therapy. However, peptide-drug conjugates (PDCs) offer several advantages over ADCs, including more accessible industrial synthesis, versatile functionalization, high tissue penetration, and rapid clearance with low immunotoxicity. These factors position PDCs as up-and-coming drug candidates for future cancer therapy. Despite their potential, PDCs face challenges such as poor pharmacokinetic properties and low bioactivity, which hinder their clinical development. How to design PDCs to meet clinical needs is a big challenge and urgent to resolve. In this review, we first carefully analyzed the general consideration of successful PDC design learning from ADCs. Then, we summarised the basic functions of each component of a PDC construct, comprising of peptides, linkers and payloads. The peptides in PDCs were categorized into three types: tumor targeting peptides, cell penetrating peptide and self-assembling peptide. We then analyzed the potential of these peptides for drug delivery, such as overcoming drug resistance, controlling drug release and improving therapeutic efficacy with reduced non-specific toxicity. To better understand the potential druggability of PDCs, we discussed the pharmacokinetics of PDCs and also briefly introduced the current PDCs in clinical trials. Lastly, we discussed the future perspectives for the successful development of an oncology PDC. This review aimed to provide useful information for better construction of PDCs in future clinical applications.

Mesenchymal stem cells (MSCs) are pluripotent stem cells that have great potential in the field of regenerative medicine. Extracellular vesicles that derived from MSCs inherit the bioactive molecules, including lipids, proteins, nucleic acids, from the donate cells. With similar biological functions as MSCs, MSC-EVs show lower toxicity, better biocompatibility, stability, and less immune rejection. Therefore, MSC-EVs are emerging as a cell-free alternative therapy for MSC-based cell therapy. Here, we reviewed the characteristics of different subtype of MSC-EVs, the functional molecules in MSC-EVs for tissue repair, the potential applications of MSC-EVs for different tissue injuries in recent three years, and the clinical progress as well as the existing challenges in MSC-EV based therapy. This review would provide some insights for the future researches and clinical translation of MSC-EVs in regenerative medicine.

Summary: Background: On March 11, 2020, the World Health Organization declared its assessment of COVID-19 as a global pandemic. However, specific antiviral drugs are still unavailable, and pateints are managed by multiple complementary treatments. Methods: The electronic medical records of COVID-19 patients where basic information, complete blood count, coagulation profile, inflammatory cytokines and serum biochemical indicators in 42 patients with COVID-19 (21 of whom were treated with low molecular weight heparin (LMWH), and 21 without LMWH) that were retrospectively analyzed to compare and evaluate the effect of LMWH treatment on disease progression. Findings: 42 patients with COVID-19 treated at the hospital between February 1 and March 15, 2020, were selected for the study, of which 21 underwent LMWH treatment (LMWH group), and 21 did not (Control), during hospitalization. Changes in the percentage of lymphocytes in the LMWH group before and after LMWH treatment were significantly different from those in the control group (11·10±9·50 vs. 3·08±9·66, p =0·011, respectively). Changes in the levels of D-dimer and fibrinogen degradation products (FDP) in the LMWH group before and after LMWH treatment were significantly different from those in the control group (-2·85±3·90, -0·05±0.85, p =0·002; -9·05±13·14, -1·78±3·15, p =0·035). Strikingly, in the LMWH group, IL-6 levels were significantly reduced after LMWH treatment (47·47±58·86, 15·76±25·71, p =0·006). Besides, the changes in IL-6 levels in the LMWH group before and after LMWH treatment were significantly different from those in the control group (-32·46±65·97, 14·96±151·09, p =0·031). Interpretation: LMWH improves the coagulation dysfunction of COVID-19 patients and exerts anti-inflammatory effects by reducing IL-6 and increasing lymphocyte %. It appears that LMWH can be used as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical trial. Funding: National Natural Science Foundation of China (No. 81603037 to SC) and the National Key Research and Development Plan of China(2017YFC0909900).