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UC San Francisco Previously Published Works

Cover page of Dietary tryptophan mitigates lung ischemia-reperfusion injury in association with increased indole-3-propionate and aryl hydrocarbon receptor signaling

Dietary tryptophan mitigates lung ischemia-reperfusion injury in association with increased indole-3-propionate and aryl hydrocarbon receptor signaling

(2026)

Background

Lung ischemia-reperfusion (IR) injury drives early morbidity after lung transplantation and cardiothoracic surgery, yet targeted preventive therapies are lacking. The gut-lung axis and microbiota-derived tryptophan metabolites, including indole-3-propionate (IPA), may regulate pulmonary immunity and inflammation. We investigated whether a tryptophan-rich (Trp-Rich) diet attenuates sterile lung IR injury by increasing microbiota-derived indole metabolites and reprogramming alveolar macrophage (AM) inflammatory responses.

Methods

C57BL/6 mice receiving isocaloric tryptophan-standard (Trp-Std) or tryptophan-rich (Trp-Rich) diets underwent lung IR injury. Oxygen saturation, lung cytokines, and aryl hydrocarbon receptor (AhR) signaling readouts were evaluated. Gut microbiota was profiled by 16S rRNA sequencing, and targeted metabolomics quantified tryptophan metabolites in feces, portal vein (PV) plasma, and lung tissue. To further assess inflammatory priming in vivo, mice were additionally challenged with intratracheal lipopolysaccharide (LPS). Mechanistic studies compared IPA with related indoles in cell lines and primary human AMs, including ex vivo nutritional IR, LPS stimulation, and AhR stimulation and blockade using synthetic agonists and antagonists.

Results

Trp-Rich feeding improved post-IR oxygenation, reduced lung IL-1β, and increased pulmonary AhR-downstream gene expression. Trp-Rich diet remodeled gut microbiota, enriching for Bifidobacterium and Lactobacillus, and increasing IPA levels across feces, PV plasma, and lung tissue. In the LPS intratracheal challenge, Trp-Rich feeding reduced IL-6 levels in lung tissue and systemic plasma. Primary AMs isolated from Trp-Rich mice also showed reduced IL-1β and IL-6 release in an ex vivo nutritional IR model. Among the tested indole metabolites, IPA showed the strongest dose-dependent suppression of LPS-induced cytokines and chemokines, suppressed ex vivo nutritional IR injury, and its effects were attenuated by pharmacologic AhR blockade.

Conclusions

A Trp-Rich diet attenuated sterile lung IR injury, coinciding with gut microbiota remodeling, increased systemic and pulmonary IPA, reduced inflammatory priming, and reprogrammed AM responses. These data support diet- or microbiome-directed strategies targeting IPA-AhR signaling to mitigate perioperative lung IR injury.

Cover page of AdcBC-dependent zinc uptake influences physiological responses in Streptococcus mutans

AdcBC-dependent zinc uptake influences physiological responses in Streptococcus mutans

(2026)

Background: Zinc is widely used in oral care products due to its antimicrobial and anti-biofilm properties; however, the molecular mechanisms by which zinc influences Streptococcus mutans (S. mutans) physiology remain incompletely understood. The AdcABC system is the primary high-affinity zinc transporter in S. mutans. We investigated whether loss of adcBC is associated with altered physiological responses in S. mutans. Material and methods: Wild-type (WT), ΔadcBC mutant, and complemented S. mutans UA159 strains were evaluated under zinc-replete and zinc-limited conditions using zinc sulphate (ZnSO4) at defined concentrations. Growth, carbohydrate utilization, acidogenicity, acid tolerance, aggregation, biofilm formation, and expression of stress response and regulatory genes were assessed. Results: Loss of adcBC impaired growth and reduced utilization of multiple carbohydrates, including key glycolytic substrates, indicating altered metabolism. Zinc supplementation restored growth but did not consistently recover redox-based metabolic activity. Expression of pflA, associated with fermentative metabolism, was reduced in the mutant. Acid tolerance was unaffected by AdcBC. Zinc enhanced aggregation and surface attachment independently of AdcBC, whereas biofilm biomass showed partial dependence on AdcBC-mediated zinc uptake. The ΔadcBC mutant also exhibited altered expression of genes involved in oxidative stress, metal homeostasis, and regulatory pathways. Conclusion: Loss of adcBC is associated with altered physiological responses in S. mutans. Zinc influences bacterial physiology through both uptake-dependent and uptake-independent mechanisms, highlighting its context-dependent role in oral environments.

Cover page of Addition of pulsed electric field ablation to SBRT for lung tumors: effect on health-related quality of life

Addition of pulsed electric field ablation to SBRT for lung tumors: effect on health-related quality of life

(2026)

INTRODUCTION: Treatment indications for oligometastatic/oligoprogressive lung tumors are growing. Safety and lack of detrimental effect on patients' quality of life are critical for novel local therapies. METHODS: We tested that the additive effect of pulsed electric field (PEF) ablation with lower-dose stereotactic body radiation therapy (SBRT) on health-related quality of life (HRQoL) as a secondary endpoint in a prospective clinical trial. FACT-Lung Cancer Subscale (FACT-LCS) and FACT-General domain surveys were collected at screening, 3 months, and 12 months. Functional clinical data included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS: Six patients with eight tumors were enrolled. Baseline well-being domain scores were: Physical 25.9 (Std Dev 2.3), Social 21.0 (Std Dev 6.9), Emotional 17.3 (Std Dev 4.7), Functional 21.2 (Std Dev 5.8), and LCS 19.4 (Std Dev 5.3). There were no significant changes following combined modality treatment in HRQoL domain scores or pulmonary function metrics after treatment. Lower EWB and SWB were associated with worse FVC and FEV1. CONCLUSION: In this small pilot study, no clinically meaningful declines in pulmonary function or patient-reported quality of life were observed at 3 months following combination therapy.

Cover page of Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice

Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice

(2026)

Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.

Cover page of Umbilical artery bypass for surgical treatment of femoral artery stenosis in a newborn: A case report

Umbilical artery bypass for surgical treatment of femoral artery stenosis in a newborn: A case report

(2026)

Femoral artery stenosis is a rare but serious complication of arterial puncture in neonates, and surgical revascularization is challenging due to small vessel size. We report the case of a premature newborn with limb-threatening ischemia from femoral artery stenosis treated using the native umbilical artery as an autologous bypass graft. The umbilical artery was mobilized, tunneled, and anastomosed distal to the stenosis, restoring perfusion. Postoperative Doppler confirmed graft patency and resolution of ischemia. The patient later died from unrelated respiratory complications. This case highlights the technical feasibility of umbilical artery bypass for neonatal limb salvage and underscores the vulnerability of premature infants.

Cover page of Active Surveillance of Ductal Carcinoma In-Situ

Active Surveillance of Ductal Carcinoma In-Situ

(2026)

Purpose of ReviewTailoring treatment strategies to the biological features of invasive disease and the individual needs and preference of each patient has transformed the way we manage breast cancer. This article calls for a similar shift in the management paradigm of ductal carcinoma in situ (DCIS) from a uniform treatment model toward a risk-stratified stepwise approach that aligns with the heterogeneous nature of the disease to avoid overtreatment.Recent FindingsMost DCIS lesions are hormone receptor positive, and only a subset have a risk for progression to invasive cancer. Early results from observational and clinical studies indicate that active surveillance is a safe and feasible alternative to upfront surgical treatment for low-risk DCIS. Ongoing clinical trials like RECAST will further inform and refine strategies for optimal management of this condition.SummaryThe integration of risk-adapted management strategies, endocrine risk-reducing interventions, and advanced imaging modalities into active surveillance protocols hold significant potential to reduce overtreatment and personalize care for patients with DCIS. Early data from clinical trials support the notion that providing a period of active surveillance is safe and offers a critical assessment window during which DCIS treatment can be individualized. Strengthening the evidence base to support the adoption of active surveillance as an initial approach in the management of DCIS is an important clinical priority.

Cover page of Fathers’ Presence Makes a Difference During Children’s Evening Meals

Fathers’ Presence Makes a Difference During Children’s Evening Meals

(2026)

This observational study used descriptive analysis to improve understanding of the relationship between fathers’ presence or absence, the occurrence of mothers’ feeding practices, and child eating behaviors at evening meals. Participants were 141 Mexican-origin families with children aged 8 to 10 years. We coded behavioral observations of video-recorded meals. Three parental feeding practices were established a priori : (1) pressure to eat, (2) restriction of amount of food, and (3) positive involvement in child’s meals. Additionally, we identified child eating behaviors and food eaten. Fewer mothers engaged in certain types of positive involvement in child’s meals when fathers were present at the meals, compared to when fathers were absent. Regarding child eating behaviors, when fathers were present, more children engaged in positive talk about food, compared to when fathers were absent. Additionally, when fathers were present, more children ate grains and fewer ate fruit, compared to when fathers were absent. Family mealtime with Mexican American children may provide an opportunity for fathers, alongside mothers, to communicate about and participate in children’s food consumption. Research on obesity in families should include a focus on fathers’ feeding practices, such as positive involvement in a child’s meals, that may complement mothers’ feeding practices.

Cover page of Secondhand smoke exposure at home and school absenteeism among children in the United States: national estimates of attributable missed school days

Secondhand smoke exposure at home and school absenteeism among children in the United States: national estimates of attributable missed school days

(2026)

Objective: The number of missed school days attributable to secondhand smoke (SHS) exposure at home among U.S. children has not been quantified. We estimated the association between SHS exposure at home and school absenteeism and derived national estimates of SHS-attributable missed school days. Methods: We analyzed data from the 2016-2024 National Survey of Children's Health for U.S. children aged 6-11 years. Propensity score weighting and two-part models were used to estimate the association between SHS exposure at home and school absenteeism. National estimates of SHS-attributable missed school days were derived by combining model-based attributable fractions with national public school enrollment data. Results: SHS exposure at home was associated with both a higher likelihood of missing school and a greater number of missed school days among children with any absence. In 2024, an estimated 266,008 (95% CI: 139,627, 392,390) missed school days were attributable to SHS exposure at home nationwide, corresponding to 0.95 additional missed school days per exposed child (95% CI: 0.56, 1.34). Conclusions: This study provides the first national estimates of SHS-attributable missed school days among U.S. children. These findings suggest that reducing children's SHS exposure may further improve school attendance and promote more efficient use of educational resources.

Cover page of Student Navigators Help UCSF Primary Care Patients Access Behavioral Health Care in the Context of Insurance and Other Barriers

Student Navigators Help UCSF Primary Care Patients Access Behavioral Health Care in the Context of Insurance and Other Barriers

(2026)

Background: At the University of California, San Francisco (UCSF), college students in the Patient Support Corps learn by helping patients navigate their care. This report focuses on how Patient Support Corps students help patients whose primary care physicians referred them to UCSF’s Integrated Behavioral Health program. We summarize the disposition of these primary care physician referrals. We also describe programmatic efforts to assure that UCSF connects all referrals to behavioral health care, whether at UCSF or externally. Methods: We counted the referrals to UCSF’s Integrated Behavioral Health program between August 2025 and May 2026. Then we determined the number of patients scheduled for care at UCSF, along with the barriers to successful scheduling. We ascertained what support the program’s staff and student navigators were able to provide patients not scheduled for care at UCSF. Student navigators also reflected on their efforts to promote equitable access to behavioral health. Results: We identified 3,568 referrals. Of these, program staff and student navigators scheduled or were in the process of scheduling 2,735 (77%) for care at UCSF. Of the 923 (23%) referrals not scheduled, 546 (59%) prescribed longer-term care than the 8-13 sessions offered by UCSF Integrated Behavioral Care. Another 302 (33%) referrals prescribed 8-13 sessions, but the patient’s home clinic had no psychiatrists or psychotherapists on staff. The remaining 75 (8%) referrals prescribed 8-13 sessions, but UCSF did not accept the patient’s insurance. For the 923 unsuccessful referrals, UCSF program staff and student navigators connected the patients with community-based services within a mean of 1.5 days. These community-based services ranged from local clinics for in-person sessions to tele-health providers for virtual visits. Students reflected on how they learned about barriers to care (e.g. technology, language, health literacy, illness, disability, and provider eligibility limits) while helping patients overcome these barriers. Conclusions: Student interns helped expand access to behavioral health care for patients dealing with insurance limitations, workforce shortages, and other system and patient-level barriers. In quickly connecting patients with community-based services, students helped reduce gaps and delays in accessing care. Students reflected that their interactions with patients (via patient portal messages or telephone) led to a more empathic understanding of what patients experience upon being referred for behavioral health. Based on these front-line interactions, students are now suggesting changes to the referral workflow to improve patient experience.