Cancer immunotherapy has made breakthrough progress in cancer treatment. However, only a subset of patients benefits from immunotherapy. Given their unique structure, composition, and interactions with the immune system, carbon nanomaterials have recently attracted tremendous interest in their roles as modulators of antitumor immunity. Here, we focused on the latest advances in the immunological effects of carbon nanomaterials. We also reviewed the current preclinical applications of these materials in cancer therapy. Finally, we discussed the challenges to be overcome before the full potential of carbon nanomaterials can be utilized in cancer therapies to ultimately improve patient outcomes.

Epigenetic remodeling and metabolic reprogramming, two well-known cancer hallmarks, are highly intertwined. In addition to their abilities to confer cancer cell growth advantage, these alterations play a critical role in dynamically shaping the tumor microenvironment and antitumor immunity. Recent studies point toward the interplay between epigenetic regulation and metabolic rewiring as a potentially targetable Achilles’ heel in cancer. In this review, we explore the key metabolic mechanisms that underpin the immunomodulatory role of AT-rich interaction domain 1A (ARID1A), the most frequently mutated epigenetic regulator across human cancers. We will summarize the recent advances in targeting ARID1A-deficient cancers by harnessing immune-metabolic vulnerability elicited by ARID1A deficiency to stimulate antitumor immune response, and ultimately, to improve patient outcome.

The COVID-19 pandemic remains an ongoing global health threat, yet effective treatments are still lacking. This has led to a high demand for complementary/alternative medicine, such as Chinese herbal medicines for curbing the COVID-19 pandemic. Given the dual anticancer and antiviral activities of many herbal drugs, they may hold a multifaceted potential to tackle both cancer and SARS-CoV-2. Triptolide is the major bioactive compound isolated from Tripterygium wilfordii Hook F (TwHF), a traditional Chinese medicinal herb recognized for its beneficial pharmacological properties in many diseases, including cancer and viral infection. However, its application in the clinic has been greatly limited due to its toxicity and poor water solubility. Here, from a screen of a natural compound library of Chinese Pharmacopoeia, we identified triptolide as a top candidate to inhibit cell entry of SARS-CoV-2. We demonstrated that triptolide robustly blocked viral entry at nanomolar concentrations in cellular models, with broad range activity against emerging Omicron variants of SARS-CoV-2. Mechanistically, triptolide disrupted the interaction of SARS-CoV-2 spike protein with its receptor ACE2. Furthermore, we synthesized water-soluble, triptolide-derived carbon quantum dots. Compared to triptolide, these highly biocompatible nanomaterials exhibited prominent antiviral capabilities against Omicron variants of SARS-CoV-2 with less cytotoxicity. Finally, we showed that triptolide-derived carbonized materials excelled in their anticancer properties compared to triptolide and Minnelide, a water-soluble analog of triptolide. Together, our results provide a rationale for the potential development of triptolide-carbonized derivatives as a promising antiviral candidate for the current pandemic and future outbreaks, as well as anticancer agents.

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of brain tumors, but the role of PRMT1 in medulloblastoma, the most common malignant pediatric brain tumor, remains unexplored. By examining the publicly available databases of pediatric brain tumor collection, we found that PRMT1 was predominantly expressed in medulloblastomas across all the pediatric brain tumors and that the high-level expression of PRMT1 correlated with poor survival of medulloblastoma patients. To determine the role of PRMT1 in medulloblastoma cells, we established an inducible knockdown system and demonstrated that PRMT1 depletion decreased medulloblastoma cell proliferation and induced cell apoptosis. Furthermore, the diamidine compounds, previously shown to exhibit selective PRMT1 inhibition, suppressed medulloblastoma cell viability in a dose-dependent manner. Finally, we observed induction of medulloblastoma cell apoptosis by the potent diamidine compounds at low micromolar concentrations. Together, our results suggest that PRMT1 could be an actionable therapeutic target in medulloblastoma.

Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite the escalating global prevalence, there is currently no definitive predisposition test available for this condition. Among the genetic causes, variations in the mitochondrial DNA (mtDNA) are increasingly recognized as a crucial contributor to the development of PCOS. However, cross-ethnic analysis of these mutations is lacking. To fill in this gap, our objective is to identify new maternal genetic risk factors associated with PCOS by investigating the mitochondrial transfer RNA (mt-tRNA) genes in PCOS patients from Pakistan and to compare these mutations to those in patients from other ethnic groups.Methods: DNA was extracted from saliva samples of patients. Primers were designed for the amplification of all of 22 mt-tRNA genes, and PCR was employed under defined conditions. Subsequently, Sanger sequencing was employed to decipher the sequences of mt-tRNA genes. Following sequencing, mt-tRNA genes underwent mutation analysis. Finally, we utilized MitoTIP (Mitochondrial tRNA Informatics Predictor) to identify variations in mt-tRNA genes.Results: In a cohort of 64 Pakistani patients with PCOS, our analysis unveiled eight variants in five mt-tRNA genes including MT-TH, MT-TL2, MT-TS1, MT-TS2, and MT-TT genes. All of these variants have not been previously reported in PCOS except one we have recently identified in a Pakistani patient with PCOS. Interestingly, most of these mt-tRNA genes carry variants found in patients with PCOS across distinct ethnic groups. Furthermore, these mutations occurred in highly conserved nucleotides of tRNA, essential for ensuring the stability and biochemical functionality of mt-tRNA. Finally, the pathogenic potential of these variations was assessed by in silico analysis. The pathogenicity prediction of these variants suggests their potential impact on mitochondrial dysfunction that was responsible for the clinical phenotypes of PCOS.Conclusion: Our study identified novel variations in mt-tRNA genes in Pakistani women with PCOS. To our knowledge, this is the first report comparing mutations of mt-tRNA genes in PCOS patients across different ethnic groups. Our data revealed common mt-tRNA genes carrying PCOS-associated mutations that may be specific to certain ethnic populations. Together, our work provides new insights into the role of mt-tRNA genes in mitochondrial dysfunction underlying the pathophysiology of PCOS, highlighting mt-tRNA mutations as potential factors for future predisposition tests and more effective therapies for this globally prevalent condition.

Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologically active compounds in immuno-oncology may open new avenues for more effective cancer therapies. In this review, we explore how natural compounds modulate the epigenetic machinery to shape antitumor immune response, highlighting the promise offered by the Mother Nature that could be exploited therapeutically to improve outcomes for cancer patients.