Circadian rhythms of macrophages are altered by the acidic tumor microenvironment.

Tumor-associated macrophages (TAMs) are prime therapeutic targets due to their pro-tumorigenic functions, but varying efficacy of macrophage-targeting therapies highlights our incomplete understanding of how macrophages are regulated within the tumor microenvironment (TME). The circadian clock is a key regulator of macrophage function, but how circadian rhythms of macrophages are influenced by the TME remains unknown. Here, we show that conditions associated with the TME such as polarizing stimuli, acidic pH, and lactate can alter circadian rhythms in macrophages.

HIV Self-Testing for Efficient PrEP Delivery Is Highly Acceptable and Feasible in Public Health HIV Clinics in Kenya: A Mixed Methods Study.

HIV self-testing (HIVST) has the potential to reduce barriers associated with clinic-based preexposure prophylaxis (PrEP) delivery. We conducted a substudy nested in a prospective, pilot implementation study evaluating patient-centered differentiated care services. Clients chose either a blood-based or oral fluid HIVST kit at the first refill visit.

Effect of differentiated direct-to-pharmacy PrEP refill visits supported with client HIV self-testing on clinic visit time and early PrEP continuation.

Introduction: Delivery of oral pre-exposure prophylaxis (PrEP) is being scaled up in Africa, but clinic-level barriers including lengthy clinic visits may threaten client continuation on PrEP.

Methods: Between January 2020 and January 2022, we conducted a quasi-experimental evaluation of differentiated direct-to-pharmacy PrEP refill visits at four public health HIV clinics in Kenya. Two clinics implemented the intervention package, which included direct-to-pharmacy for PrEP refill, client HIV self-testing (HIVST), client navigator, and pharmacist-led rapid risk assessment and dispensing.

Circadian rhythms of macrophages are altered by the acidic pH of the tumor microenvironment.

Macrophages are prime therapeutic targets due to their pro-tumorigenic and immunosuppressive functions in tumors, but the varying efficacy of therapeutic approaches targeting macrophages highlights our incomplete understanding of how the tumor microenvironment (TME) can influence regulation of macrophages. The circadian clock is a key internal regulator of macrophage function, but how circadian rhythms of macrophages may be influenced by the tumor microenvironment remains unknown. We found that conditions associated with the TME such as polarizing stimuli, acidic pH, and elevated lactate concentrations can each alter circadian rhythms in macrophages.

MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis.

The molecular circadian clock, which controls rhythmic 24-hour oscillation of genes, proteins, and metabolites in healthy tissues, is disrupted across many human cancers. Deregulated expression of the MYC oncoprotein has been shown to alter expression of molecular clock genes, leading to a disruption of molecular clock oscillation across cancer types. It remains unclear what benefit cancer cells gain from suppressing clock oscillation, and how this loss of molecular clock oscillation impacts global gene expression and metabolism in cancer.