Protein tyrosine phosphatase 1B (PTP1B) is a critical negative modulator of insulin signaling and has attracted considerable attention in treating type 2 diabetes mellitus (T2DM). Low-molecular-weight polymannuronic acid phosphate (LPMP) was found to be a selective PTP1B inhibitor with an IC₅₀ of 1.02 ± 0.17 μM. Cellular glucose consumption was significantly elevated in insulin-resistant HepG2 cells after LPMP treatment. LPMP could alleviate oxidative stress and endoplasmic reticulum stress, which are associated with the development of insulin resistance. Western blot and polymerase chain reaction (PCR) analysis demonstrated that LPMP could enhance insulin sensitivity through the PTP1B/IRS/Akt transduction pathway. Furthermore, animal study confirmed that LPMP could decrease blood glucose, alleviate insulin resistance, and exert hepatoprotective effects in diabetic mice. Taken together, LPMP can effectively inhibit insulin resistance and has high potential as an anti-diabetic drug candidate to be further developed.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS–5) and its N-acetylated derivative (N–5) showed the best protective activity. Pretreatment with COS–5 or N–5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N–5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.

Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown cardiac function benefits. Here, we designed a pH-responsive PSS-loaded nanoparticle drug delivery system. It was self-assembled by negatively charged PSS with positively charged trimethyl chitosan glycocholic acid (TMC-GA) via electrostatic interaction, and further stabilized the nanoparticles with Hydroxypropyl methylcellulose phthalate (HP55) excipients. The prepared TMC-GA/HP55@PSS nanoparticles were spherical, with a mean particle size of 361.5 ± 1.26 nm, zeta potential of −30.3 ± 0.9 mV, and encapsulation efficiency of 92.52 ± 2.4%. In vitro release study demonstrated the pH-responsive property of TMC-GA/HP55@PSS under intestinal conditions and facilitated nanoparticles absorption in the intestinal epithelium. In vitro experiments confirmed the biocompatibility of PSS and its ability to improve myocardial cell hypertrophy. In vivo, both PSS and its nanoparticles significantly ameliorated pressure overload–induced cardiac hypertrophy in mice, with TMC-GA/HP55@PSS exhibiting better cardioprotective efficacy. This study is the first to integrate pH-responsiveness and bile acid transport-mediated uptake into PSS nanocarrier systems. The findings provide valuable data and enlightenment for designing novel formulations and expanding the clinical applications of PSS.

Genital herpes is a common sexually transmitted disease mainly caused by herpes simplex virus type 2 (HSV-2), which can increase the risk of HIV transmission and is a major health problem in the world. Thus, it is of great significance to develop new anti-HSV-2 drugs with high efficiency and low toxicity. In this study, the anti-HSV-2 activities of PSSD, a marine sulfated polysaccharide, was deeply explored both in vitro and in vivo. The results showed that PSSD had marked anti-HSV-2 activities in vitro with low cytotoxicity. PSSD can directly interact with virus particles to inhibit the adsorption of virus to the cell surface. PSSD may also interact with virus surface glycoproteins to block virus-induced membrane fusion. Importantly, PSSD can significantly attenuate the symptoms of genital herpes and weight loss in mice after gel smear treatment, as well as reducing the titer of virus shedding in the reproductive tract of mice, superior to the effect of acyclovir. In summary, the marine polysaccharide PSSD possesses anti-HSV-2 effects both in vitro and in vivo, and has potential to be developed into a novel anti-genital herpes agent in the future.