Peptide- and protein-based therapeutics offer realized and potential benefits to health, due to their potent bioactivity, high specificity, and favorable safety characteristics. However, their widespread clinical application is constrained by inherent limitations, including rapid enzymatic degradation, poor membrane permeability, and a reliance on parenteral administration, which reduces patient adherence. To overcome these challenges, extensive research has explored non-invasive delivery strategies, including topical, transdermal, and oral formulations. Despite promising advances in these delivery strategies, they are yet to overcome substantial biological and physicochemical barriers in peptide and protein therapeutics, such as enzymatic degradation in the gastrointestinal tract, limited epithelial transport, and inherently low systemic bioavailability. This review provides a comprehensive and up-to-date analysis of the structural and physiological barriers influencing peptide and protein bioavailability and therapeutic efficacy. It critically examines key challenges associated with various administration routes, including topical, transdermal, oral (including delivery targeting the brain), and others. Furthermore, it explores innovative strategies to enhance peptide and protein stability and bioavailability, including chemical modifications, enzyme inhibitors, penetration enhancers, physical delivery technologies, and advanced nanoparticulate formulations. Additionally, emerging trends in formulation optimization, regulatory considerations, and translational pathways for clinical implementation are discussed. By addressing these critical challenges and highlighting recent advances, this review serves as a roadmap for the development of next-generation peptide and protein therapeutics with improved stability and efficacy, and enhanced patient adherence, which is needed to fully realize the true potential of this class of therapeutics.

Lycium barbarum polysaccharide (LBP) has traditionally been used in Chinese medicine as a chief ingredient of Lycium barbarum (wolf berry/goji berry) for the treatment of various diseases with the symptoms of frequent drinking and urination. This study was conducted as a randomized, controlled clinical trial. A total of 67 patients with type 2 diabetes (30 in control group and 37 in LBP group) were enrolled in this prospective, randomized, double-blind study (administration at 300mg/day body weight). In order to observe the hypoglycemic and lipid-lowering activity of LBP in patients with type 2 diabetes after dinner, various tests were conducted between control and LBP intervention groups in 3 months. Although, the study had small sample size and short follow-up, significant findings were observed. The results of our study indicated a remarkable protective effect of LBP in patients with type 2 diabetes. Serum glucose was found to be significantly decreased and insulinogenic index increased during OMTT after 3 months administration of LBP. LBP also increased HDL levels in patients with type 2 diabetes. It showed more obvious hypoglycemic efficacy for those people who did not take any hypoglycemic medicine compared to patients taking hypoglycemic medicines. This study showed LBP to be a good potential treatment aided-agent for type 2 diabetes.

Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 (p = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of Akkermansia muciniphila and Roseburia, and the relative abundance of Dialister, Butyrivibrio, and Paraprevotella, and decreased unclassified f-Sutterellaceae. In the oat group, Bifidobacterium abundance was negatively correlated with LDL-C (p = 0.01, r = −0.31) and, TC and LDL-C were negatively correlated to Faecalibacterium prausnitzii (p = 0.02, r = −0.29; p = 0.03, r = −0.27, respectively). Enterobacteriaceae, Roseburia, and Faecalibacterium prausnitzii were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid (p = 0.02, r = −0.25) and total triglyceride (TG) was positively correlated to isovaleric acid (p = 0.03, r = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. Akkermansia muciniphila, Roseburia, Bifidobacterium, and Faecalibacterium prausnitzii, and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.

To assess the associations between maternal body mass index (BMI) as well as gestational weight gain (GWG) and pregnancy outcomes in women with gestational diabetes mellitus (GDM). This is a retrospective analysis involving 832 nulliparous women complicated with GDM. Multivariate logistic and restricted cubic logistic regression were used to investigate the association of interest. Overall, 178 (21.4%) women were overweight or obese, and 298 (35.2%) exhibited excessive GWG. Compared with women of normal weight, high pre-pregnancy BMI resulted in a higher risk of cesarean section with an adjusted odds ratio of 1.95 (95% confidence interval being 1.29–2.96) for overweight group and 3.26 (1.57–6.76) for obese group. Similarly, the respective aORs were 4.10 (1.56–10.81) and 9.78 (2.91–32.85) for gestational hypertension, 2.02 (1.05–3.88) and 8.04 (3.46–18.66) for macrosomia, 2.14 (1.40–3.26) and 3.34 (1.69–6.60) for large for gestational age (LGA). Compared with adequate GWG, excessive GWG increased the incidence of cesarean section (1.60, 1.15–2.23) and macrosomia (1.94, 1.11–3.38), while inadequate GWG reduced the incidence of LGA (0.29, 0.17–0.51). High pre-pregnancy BMI and excessive GWG were associated with higher incidence of LGA, as well as other adverse outcomes in women with GDM. Narrower guidelines on GWG might offer extra safety benefit in gestational diabetic population.

Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China.